bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure–response relationships for personal exposure to fine particulate matter (PM2·5), carbon monoxide, and black carbon and birthweight: Results from the multi-country Household Air Pollution Intervention Network (HAPIN) trial
Authors: Balakrishnan Kalpana , Steenland Kyle , Clasen Thomas , Chang Howard , Johnson Michael , Pillarisetti Ajay , Ye Wenlu , Naeher Luke P. , Diaz-Artiga Anaite , McCracken John P. , Thompson Lisa M. , Rosa Ghislaine , Kirby Miles A. , Thangavel Gurusamy , Sambandam Sankar , Mukhopadhyay Krishnendu , Puttaswamy Naveen , Aravindalochanan Vigneswari , Garg Sarada , Ndagijimana Florien , Hartinger Stella , UnderHill Lindsay , Kearns Katherine A , Campbell Devan , Kremer Jacob , Waller Lance , Jabbarzadeh Shirin , Wang Jiantong , Chen Yunyun , Rosenthal Joshua , Quinn Ashlinn , Papageorghiou Aris T. , Ramakrishnan Usha , Howards Penelope P. , Checkley William , Peel Jennifer L. ,   HAPIN Investigators
Published: August 2022

Background

Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data on exposure-response relationships are limited. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial.

Methods

We recruited 3200 pregnant women between 9 and <20 weeks of gestation. Women randomized to the intervention arm received a liquified petroleum gas (LPG) stove and fuel during pregnancy, while control arm women continued using biomass. We measured 24-hr personal exposures to particulate matter (PM2·5), carbon monoxide (CO), and black carbon (BC) once pre-intervention (baseline), twice post-intervention, and birthweight within 24 hours of birth. We examined the relationship between the average prenatal exposure and birthweight/weight-for-gestational age z-scores using multivariate-regression models.

Findings

Results showed an inter-quartile increase in average prenatal exposure to PM2.5 (74·5 μg/m3) and BC (7·3 μg/m3) was associated with a 14·8 (95% confidence interval [CI]: -28·7g, - 0·8g) and 21·9g (95% CI: -37·3g, -6·1g) reduction in birthweight and reduced weight-for-gestational age z-scores of -0·03 (95% CI: -0.06, 0·00) and -0·05 (95%CI: -0·08, -0·01) standard deviations, respectively. We found no associations for birthweight or weight-for-gestational age z-scores with CO exposures.

Interpretation

Results provide support for continuing efforts to reduce HAP exposure alongside other drivers of low birthweight in low- and middle-income countries.

Funding

The study is registered with ClinicalTrials.gov (NCT02944682) and funded by the U.S. National Institutes of Health (1UM1HL134590) in collaboration with the Bill & Melinda Gates Foundation (OPP1131279).
A comparison of the effectiveness of biologic therapies for asthma: a systematic review and network meta-analysis
Authors: Pitre Tyler , Jassal Tanvir , Angjeli Albi , Jarabana Vineeth , Nannapaneni Sricherry , Umair Ayesha , Hussain Muizz , Leung Gareth , Kirsh Sarah , Su Johnny , Desai Kairavi , Coyne Jade , Mohan Sindu , Zeraatkar Dena
Published: August 2022

Background

Trials have not directly compared biologics for the treatment of asthma.

Objective

To comparative the relative efficacy of biologics in asthma.

Methods

We searched MEDLINE, EMBASE, CENTRAL, andclinicaltrials.govfrom inception to May 31, 2022, for randomized trials addressing biologic therapies for asthma. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the GRADE approach. We present dichotomous outcomes as absolute risk differences per 1000 patients and relative risk (RR) with 95% confidence intervals (95% CI) and continuous outcomes as mean difference (MD) and 95% CI.

Results

We identified 64 trials, including 26,630 patients. For patients with eosinophilic asthma, tezepelumab (329 fewer exacerbations per 1000 [95% CI 272.6 to 366.6 fewer]) and dupilumab (319.6 fewer exacerbations per 1000 [95% CI 272.6 to 357.2 fewer]) reduce exacerbations compared to placebo (high certainty). Tezepelumab (MD 0.24 L [95% CI 0.16 to 0.32]) and dupilumab (0.25 L (95% CI 0.21 to 0.29) improve lung function (FEV1) compared to placebo (high certainty). Both tezepelumab (110.97 fewer hospital admissions per 1000 (95% CI 94.53 to 120.56 fewer) and dupilumab (97.27 fewer hospitalizations [4.11 to 124.67 fewer]) probably reduce hospital admissions compared to placebo (moderate certainty). For patients with low eosinophils, biologics probably do not improve asthma outcomes. For these patients, tezepelumab (MD 0.1 L [95% CI 0 to 0.19]) and dupilumab (MD 0.1 L [95% CI 0 to 0.20)] may improve lung function (low certainty).

Conclusion

Tezepelumab and dupilumab are effective at reducing exacerbations. For patients with low eosinophils, however, clinicians should probably be more judicious in use of biologics, including tezepelumab since they probably do not confer substantial benefit.
Quantification of metabolic niche occupancy dynamics in a Baltic Sea bacterial community
Authors: Massing Jana C. , Fahimipour Ashkaan , Bunse Carina , Pinhassi Jarone , Gross Thilo
Published: August 2022

Progress in molecular methods has enabled the monitoring of bacterial populations in time. Nevertheless, understanding community dynamics and its links with ecosystem functioning remains challenging due to the tremendous diversity of microorganisms. Conceptual frameworks that make sense of time-series of taxonomically-rich bacterial communities, regarding their potential ecological function, are needed. A key concept for organizing ecological functions is the niche, the set of strategies that enable a population to persist and define its impacts on the surroundings. Here we present a framework based on manifold learning, to organize genomic information into potentially occupied bacterial metabolic niches over time. We apply the method to re-construct the dynamics of putatively occupied metabolic niches using a long-term bacterial time-series from the Baltic Sea, the Linnaeus Microbial Observatory (LMO). The results reveal a relatively low-dimensional space of occupied metabolic niches comprising groups of taxa with similar functional capabilities. Time patterns of occupied niches were strongly driven by seasonality. Some metabolic niches were dominated by one bacterial taxon whereas others were occupied by multiple taxa, and this depended on season. These results illustrate the power of manifold learning approaches to advance our understanding of the links between community composition and functioning in microbial systems.

Importance

The increase in data availability of bacterial communities highlights the need for conceptual frameworks to advance our understanding of these complex and diverse communities alongside the production of such data. To understand the dynamics of these tremendously diverse communities, we need tools to identify overarching strategies and describe their role and function in the ecosystem in a comprehensive way. Here, we show that a manifold learning approach can coarse grain bacterial communities in terms of their metabolic strategies and that we can thereby quantitatively organize genomic information in terms of potentially occupied niches over time. This approach therefore advances our understanding of how fluctuations in bacterial abundances and species composition can relate to ecosystem functions and it can facilitate the analysis, monitoring and future predictions of the development of microbial communities.
Timing and Delivery route effects of Cecal Microbiome transplants on Salmonella Typhimurium infections in Chickens
Authors: Pottenger Sian , Watts Amyleigh , Wedley Amy , Jopson Sue , Darby Alistair C , Wigley Paul
Published: August 2022

Background

Exposure to microbes early in life has long-lasting effects on microbial community structure and function of the microbiome. However, in commercial poultry settings chicks are reared as a single-age cohort with no exposure to adult birds which can have profound effects on microbiota development and subsequent pathogen challenge. Microbiota manipulation is a proven and promising strategy to help reduce pathogen load and transmission within broiler flocks.

Results

Manipulation of the microbiota between 4 and 72 hours of hatch markedly reduces faecal shedding and colonisation with the foodborne pathogen Salmonella enterica serovar Typhimurium (ST4/74). Administration route has minimal effect on the protection conferred with fewer birds in transplant groups shown to shed ST4/74 in the faeces compared to PBS-gavaged control birds. Analysis of the microbiome following transplantation demonstrated that the relative abundance of the anti-inflammatory bacterium Faecalibacterium prausnitzii was significantly higher in CMT groups compared to PBS controls. The presence of F. prausnitzii was also shown to increase in PBS-challenged birds compared to unchallenged birds potentially indicating a role of this bacterium in limiting Salmonella infections.

Conclusions

This study highlights the efficacy of using microbiome transplants as a means to reduce colonisation and shedding of Salmonella in chickens. Effective protection can be conferred during the first few days of a chick’s life regardless of time point and traditional hatchery delivery systems are sufficient to alter the microbiome and transfer donor material. Early microbiota intervention in chickens is a promising route of pathogen control in broiler flocks in the fight to control food-borne outbreaks in the human population.
Distribution of the gyromitrin mycotoxin in the lorchel family assessed by a pre-column-derivatization and ultra high-performance liquid chromatography method
Authors: Dirks Alden C. , Mohamed Osama G. , Schultz Pamela , Miller Andrew N. , Tripathi Ashootosh , James Timothy Y.
Published: August 2022

Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) and its homologs are deadly mycotoxins produced most infamously by the lorchel (also known as false morel) Gyromitra esculenta, which is paradoxically consumed as a delicacy in some parts of the world. There is much speculation about the presence of gyromitrin in other species of the lorchel family (Discinaceae), but no studies have broadly assessed its distribution. Given the history of poisonings associated with the consumption of G. esculenta and G. ambigua, we hypothesized that gyromitrin evolved in the last common ancestor of these taxa and would be present in their descendants with adaptive loss of function in the nested truffle clade, Hydnotrya. To investigate this hypothesis, we developed a sensitive analytical derivatization method for the detection of gyromitrin using 2,4-dinotrobenzaldehyde as the derivatization reagent. In total, we analyzed 66 specimens for the presence of gyromitrin over 105 tests. Moreover, we sequenced the nuc rDNA ITS1-5.8S-ITS2 region (ITS barcode) and nuc 28S rDNA to assist in species identification and to infer a supporting phylogenetic tree. We detected gyromitrin in all tested specimens from the G. esculenta group as well as G. leucoxantha. This distribution is consistent with a model of rapid evolution coupled with horizontal transfer, which is typical for secondary metabolites. We clarified that gyromitrin production in Discinaceae is both discontinuous and more limited than previously thought. Further research is required to elucidate the gyromitrin biosynthesis gene cluster and its evolutionary history in lorchels. KEYWORDS: 2,4-dinitrobenzaldehyde, Gyromitra spp., Hydnotrya spp., Discinaceae, Pezizales, Schiff bases, UHPLC-DAD analysis
Validation of an engineered Zika virus-like particle vaccine candidate in a mosquito-mouse transmission model
Authors: Mancini Maria Vittoria , Tandavanitj Rapeepat , Ant Thomas H. , Murdochy Shivan M. , Gingell Daniel D. , Setthapramote Chayanee , Natsrita Piyatida , Kohl Alain , Sinkins Steven P. , Patel Arvind H. , De Lorenzo Giuditta
Published: August 2022

The primary route of Zika virus (ZIKV) transmission is through the bite of an infected Aedes mosquito, when it probes the skin of a vertebrate host during a blood meal. Viral particles are injected into the bite site together with mosquito saliva and a complex mixture of other components. Some of them are shown to play a key role in the augmentation of the arbovirus infection in the host, with increased viremia and/or morbidity. This vector-derived contribution to the infection is not usually considered when vaccine candidates are tested in preclinical animal models. In this study, we performed a preclinical validation of a promising ZIKV vaccine candidate in a mosquito-mouse transmission model using both Asian and African ZIKV lineages. Mice were immunized with engineered ZIKV virus-like particles and subsequently infected through the bite of ZIKV-infected Ae. aegypti mosquitoes. Despite a mild increase in viremia in mosquito-infected mice compared to those infected through traditional needle injection, the vaccine protected the animals from developing the disease and strongly reduced viremia. In addition, during peak viremia, naïve mosquitoes were allowed to feed on infected vaccinated and non-vaccinated mice. Our analysis of viral titers in mosquitos showed that the vaccine was able to inhibit virus transmission from the host to the vector.

Author summary

Zika is a mosquito-borne viral disease, causing acute debilitating symptoms and complications in infected individuals and irreversible neuronal abnormalities in newborn children. The primary vectors of ZIKV are generally considered to be mosquitoes of the genus Aedes, in particular Aedes aegypti. Despite representing a significant public health burden with a widespread transmission in many regions of the world, Zika remains a neglected disease with no effective antiviral therapies or approved vaccines to control and prevent infections. The efficacy of several promising candidate vaccines is however under investigation, mainly through artificial infections (i.e. needle-mediated injections of the virus) in animal models, while it is known that components of the mosquito bite lead to an enhancement of viral infection and spread. In this study, we have also included mosquitoes as viral vectors, demonstrating that the ability of a promising candidate vaccine to protect animals against ZIKV infections after the bite of an infected mosquito, and to also prevent its further transmission. These findings represent an additional crucial step for the development of an effective prevention tool for clinical use.

Graphical abstract
TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
Authors: Shetty Sunil , Hofstetter Jon , Battaglioni Stefania , Ritz Danilo , Hall Michael N.
Published: August 2022

Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells preserve a small pool of dormant ribosomes under nutrient-limited conditions. The regulation of dormant ribosomes is poorly characterized. Here, we show that upon inhibition of TORC1 by rapamycin or nitrogen starvation, Stm1 (suppressor of target of Myb protein 1) forms non-translating, dormant 80S ribosomes. Furthermore, Stm1-bound 80S ribosomes are protected from proteasomal degradation. Upon re-feeding, TORC1 directly phosphorylates and inhibits Stm1, thereby reactivating translation. Finally, SERBP1 (SERPINE1 mRNA binding protein), a mammalian ortholog of Stm1, forms dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. Thus, TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner via a ribosome preservation factor.
Sex differences in early and term placenta are conserved in adult tissues
Authors: Olney Kimberly C. , Plaisier Seema B. , Phung Tanya N. , Silasi Michelle , Perley Lauren , O’Bryan Jane , Ramirez Lucia , Kliman Harvey J. , Wilson Melissa A.
Published: August 2022

Background

Pregnancy complications vary based on the fetus’s genetic sex, which may, in part, be modulated by the placenta. Further, developmental differences early in life can have lifelong health outcomes. Yet, sex differences in gene expression within the placenta at different time points throughout pregnancy and comparisons to adult tissues remains poorly characterized.

Methods

Here, we collect and characterize sex differences in gene expression in term placentas ( ≥ 36.6 weeks; 23 male XY and 27 female XX). These are compared with sex differences in previously collected first trimester placenta samples and 42 non-reproductive adult tissues from GTEx.

Results

We identify 268 and 53 sex differentially expressed genes in the uncomplicated late first trimester and term placentas, respectively. Of the 53 sex differentially expressed genes observed in the term placentas, 31 are also sex differentially expressed genes in the late first trimester placentas. Furthermore, sex differences in gene expression in term placentas are highly correlated with sex differences in the late first trimester placentas. We found that sex differential gene expression in the term placenta is significantly correlated with sex differences in gene expression in 42 non-reproductive adult tissues (correlation coefficient ranged from 0.892 to 0.957), with the highest correlation in brain tissues. Sex differences in gene expression were largely driven by gene expression on the sex chromosomes. We further show that some gametologous genes (genes with functional copies on X and Y) will have different inferred sex differences if the X-linked gene expression in females is compared to the sum of the X-linked and Y-linked gene expression in males.

Conclusions

We find that sex differences in gene expression are conserved in late first trimester and term placentas and that these sex differences are conserved in adult tissues. We demonstrate that there are sex differences associated with innate immune response in late first trimester placentas but there is no significant difference in gene expression of innate immune genes between sexes in healthy full term placentas. Finally, sex differences are predominantly driven by expression from sex-linked genes.

Highlights

Sex differences in gene expression in late first trimester placentas are positively correlated with sex differences in gene expression in full term placentas; sex differences develop early and are maintained.

Sex differences in gene expression on the sex chromosomes in the placenta are correlated to sex differences in adult tissues.

Sex-linked gametolog genes require additional methodological approaches for accurate quantification.
Comprehensive chromatin proteomics resolves functional phases of pluripotency
Authors: Ugur Enes , de la Porte Alexandra , Bultmann Sebastian , Drukker Micha , Mann Matthias , Wierer Michael , Leonhardt Heinrich
Published: August 2022

The establishment of cellular identity is driven by transcriptional and epigenetic regulation exerted by the components of the chromatin proteome - the chromatome. However, chromatome composition and its dynamics in functional phases of pluripotency have not been comprehensively analyzed thus limiting our understanding of these processes. To address this problem, we developed an accurate mass spectrometry (MS)-based proteomic method called Chromatin Aggregation Capture (ChAC) followed by Data-Independent Acquisition (DIA) to analyze chromatome reorganizations during the transition from ground to formative and primed pluripotency states. This allowed us to generate a comprehensive atlas of proteomes, chromatomes, and chromatin affinities for the three pluripotency phases, revealing the specific binding and rearrangement of regulatory complexes. The technical advances, the comprehensive chromatome atlas, and the extensive analysis reported here provide a foundation for an in-depth understanding of mechanisms that govern the phased progression of pluripotency and changes of cellular identities in development and disease.
Auditory corticofugal neurons transmit auditory and non-auditory information during behavior
Authors: Ford Alexander N. , Czarny Jordyn E. , Rogalla Meike M. , Quass Gunnar L. , Apostolides Pierre F.
Published: August 2022

Layer 5 pyramidal neurons of sensory cortices project “corticofugal” axons to myriad sub-cortical targets, thereby broadcasting high-level signals important for perception and learning. Recent studies suggestdendritic Ca2+spikesas key biophysical mechanisms supporting corticofugal neuron function: These long-lasting events drive burst firing, thereby initiating uniquely powerful signals to modulate sub-cortical representations and trigger learning-related plasticity. However, the behavioral relevance of corticofugal dendritic spikes is poorly understood. We shed light on this issue using 2-photon Ca2+imaging of auditory corticofugal dendrites as mice of either sex engage in a GO/NO-GO sound-discrimination task.

Unexpectedly, only a minority of dendritic spikes were triggered by behaviorally relevant sounds under our conditions. Task related dendritic activity instead mostly followed sound cue termination and co-occurred with mice’s instrumental licking during the answer period of behavioral trials, irrespective of reward consumption. Temporally selective, optogenetic silencing of corticofugal neurons during the trial answer period impaired auditory discrimination learning. Thus, auditory corticofugal systems’ contribution to learning and plasticity may be partially non-sensory in nature.

Significance Statement

The auditory cortex sends a massive “feedback” projection to the inferior colliculus (IC) which controls IC neuron plasticity and some types of perceptual learning. Precisely what signals are fed back during behavior is unclear. Using multiphoton imaging of auditory cortico-collicular neurons as mice engage in a sound discrimination task, we find that activity coincides more with mice’s instrumental actions rather than sound cues. Dendritic Ca2+spikes and burst firing contributed to this non-auditory activity, which is notable given that dendritic spikes instruct synaptic plasticity in many other circuits. Accordingly, optogenetic silencing of corticofugal neurons during mice’s instrumental actions impaired discriminative learning. Auditory corticofugal neurons may thus transmit significant non-auditory information that contributes to learning-related plasticity.
Dnmt3bascoordinates transcriptional induction and alternative exon inclusion to promote catalytically active Dnmt3b expression
Authors: Dar Mohd Saleem , Mensah Isaiah K , He Ming , McGovern Sarah , Hall Mark C , Whitlock Hannah Christian , Bippus Nina Elise , Ceminsky Madison , Emerson Martin L , Tan Hern J , Gowher Humaira
Published: August 2022

During mammalian embryogenesis, DNMT3B activity is critical for the genome-wide establishment of DNA methylation. Using naïve ESC differentiation as a model, we elucidated the mechanism by which lncRNA,Dnmt3bas,controls the inducible expression and alternative splicing ofDnmt3b. Our data showed thatDnmt3basknockdown increased transcriptional induction and decreased H3K27me3 at Dnmt3b cis-regulatory elements post-differentiation. Notably, transcriptional induction ofDnmt3bwas accompanied by exon inclusion, switching the major isoform from catalytically inactiveDnmt3b6to the activeDnmt3b1. WhileDnmt3basoverexpression attenuatedDnmt3binduction, it increased theDnmt3b1:Dnmt3b6ratio. This observation was explained by a specific interaction ofDnmt3baswith hnRNPL, which promotes exon inclusion. These data suggest thatDnmt3bascoordinates alternative splicing and transcriptional induction of Dnmt3b by facilitating the interaction of hnRNPL and RNA Pol II at the Dnmt3b promoter. This two-pronged mechanism would tightly control DNMT3B activity, ensuring the fidelity and specificity ofde novoDNA methylation during development.
Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic marks
Authors: Cassiano Larissa M. G. , Silva Vanessa C. , Oliveira Marina S. , Prado Bárbara V. O. , Cardoso Cristianne G. , Salim Anna C. M. , Franco Gloria R. , D’Almeida Vânia , Francisco Saionara C. , Coimbra Roney S.
Published: August 2022

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, raising the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic marks in leukocytes favorably regulates central components of COVID-19 physiopathology.

Teaser

B12 has great potential as an adjuvant drug for alleviating inflammation in COVID-19.
Acetylsalicylic acid and Salicylic acid inhibit SARS-CoV-2 replication in precision-cut lung slices
Authors: Geiger Nina , König Eva-Maria , Oberwinkler Heike , Roll Valeria , Diesendorf Viktoria , Fähr Sofie , Obernolte Helena , Seewald Katherina , Wronski Sabine , Steinke Maria , Bodem Jochen
Published: August 2022

Aspirin, with its active compound acetylsalicylic acid (ASA), shows antiviral activity against rhino- and influenza viruses and at high concentrations. We sought to investigate whether ASA and its metabolite salicylic acid (SA) inhibit SARS-CoV-2 since it might use similar pathways to influenza viruses. The compound-treated cells were infected with SARS-CoV-2. Viral replication was analyzed by RTqPCR. The compounds suppressed SARS-CoV-2 replication in cell culture cells and in a patient-near replication system using human precision-cut lung slices by two orders of magnitude. The compounds did not interfere with viral entry but led to lower viral RNA expression after 24 h.
Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism
Authors: Bussi Claudio , Heunis Tiaan , Pellegrino Enrica , Bernard Elliott M. , Bah Nourdine , dos Santos Mariana Silva , Santucci Pierre , Aylan Beren , Rodgers Angela , Fearns Antony , Mitschke Julia , Moore Christopher , MacRae James I. , Greco Maria , Reinheckel Thomas , Trost Matthias , Gutierrez Maximiliano G.
Published: August 2022

Transient lysosomal damage after infection with cytosolic pathogens or silica crystals uptake results in protease leakage. Whether limited leakage of lysosomal contents into the cytosol affects the function of cytoplasmic organelles is unknown. Here, we show that sterile and non-sterile lysosomal damage triggers a cell death independent proteolytic remodelling of the mitochondrial proteome in macrophages. Mitochondrial metabolic reprogramming required lysosomal leakage of Cathepsin B and Cathepsin L and was independent of proteasome degradation and mitophagy. In a mouse model of endomembrane damage, metabolic analysis confirmed that in vivo, live lung macrophages that internalised crystals displayed impaired mitochondrial function and increased glycolytic and lipid metabolism. Single-cell RNA-sequencing analysis of bronchoalveolar lavage revealed that lysosomal damage skewed metabolic and immune responses primarily in CD36+/LIPA+ and Krt79+/Car4+ subsets of alveolar macrophages. Importantly, modulation of macrophage metabolism with 2-Deoxy- d- glucose and oxamate impacted the host response to Mycobacterium tuberculosis (Mtb) infection in an endomembrane damage dependent manner. This work uncovers a new inter-organelle communication pathway, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprograming after endomembrane damage.
Targeting Epsins to Inhibit FGF Signaling while Potentiating TGF-β Signaling Constrains Endothelial-to-Mesenchymal-Transition in Atherosclerosis
Authors: Dong Yunzhou , Wang Beibei , Du Mulong , Zhu Bo , Cui Kui , Chan Siu-Lung , Cowan Douglas B. , Bhattacharjee Sudarshan , Shan Dan , Wong Scott , Bischoff Joyce , Linton MacRae F. , Chen Hong
Published: August 2022

BACKGROUND

Epsin endocytic adaptor proteins are implicated in the progression of atherosclerosis; however, the underlying molecular mechanisms have not yet been fully defined. In this study, we determined how epsins enhance endothelial-to-mesenchymal transition (EndoMT) in atherosclerosis and assessed the efficacy of a therapeutic peptide in a preclinical model of this disease.

METHODS

Using single cell RNA sequencing (scRNA-seq), combined with molecular, cellular, and biochemical analyses, we investigated the role of epsins in stimulating EndoMT using knock-out mouse models. The therapeutic efficacy of a synthetic peptide targeting atherosclerotic plaques was then assessed inApoe−/−mice.

RESULTS

ScRNA-seq and lineage tracing revealed that epsins 1 and 2 promote EndoMT, and the loss of endothelial epsins inhibits EndoMT marker expression as well as transforming growth factor-beta signalingin vitroand in atherosclerotic mice, which is associated with smaller lesions inApoe−/−mouse model. Mechanistically, the loss of endothelial cell epsins results in increased fibroblast growth factor receptor-1 (FGFR1) expression that inhibits TGF-β signaling and EndoMT. Epsins directly bind ubiquitinated FGFR1 through their ubiquitin-interacting motif (UIM), which results in endocytosis and degradation of this receptor complex. Consequently, administration of a synthetic UIM–containing peptide API significantly attenuates EndoMT and progression of atherosclerosis.

CONCLUSIONS

We conclude that epsins potentiate EndoMT during atherogenesis by increasing TGF-β signaling through FGFR1 internalization and degradation. Inhibition of EndoMT by reducing epsin-FGFR1 interaction with a therapeutic peptide may represent a novel treatment strategy for atherosclerosis.
Synthesis, X-ray diffraction study, analysis of intermolecular interactions and molecular docking of ethyl 1-(3-tosylquinolin-4-yl)piperidine-4-carboxylate
Authors: Vaksler Yevhenii , Hryhoriv Halyna V. , Kovalenko Sergiy M. , Perekhoda Lina O. , Georgiyants Victoriya A.
Published: August 2022

The title compound, C24H26N2O4S, can be obtained via two synthetic routes. According to our investigations, the most suitable way is by the reaction of ethyl 2-bromoacetate with sodium tosylsulfinate in dry DMF. It was crystallized from methanol into the monoclinic P21/n space group with a single molecule in the asymmetric unit. Hirshfeld surface analysis was performed to define the hydrogen bonds and analysis of the two-dimensional fingerprint plots was used to distinguish the different types of interactions. Two very weak non-classical C—H...O hydrogen bonds were found and the contributions of short contacts to the Hirshfeld surface were determined. Molecules form an isotropic network of intermolecular interactions according to an analysis of the pairwise interaction energies. A molecular docking study evaluated the interactions in the title compound with the active centers of macromolecules of bacterial targets (Staphylococcus aureus DNA Gyrase PDB ID: 2XCR, Mycobacterium tuberculosis topoisomerase II PDB ID: 5BTL, Streptococcus pneumoniae topoisomerase IV PDB ID: 4KPF) and revealed high affinity towards them that exceeded the reference antibiotics of the fluoroquinolone group.
Fabrication and microstructural characterization of Al-SiC based functionally graded disk
Authors: Madan Royal , Bhowmick Shubhankar
Published: August 2022

Purpose

The purpose of this study is to investigate the performance of disks that can be increased by functionally grading the disk in the radial direction; there are several but distinct categories of literature that pertain to the fabrication of disk in the thickness direction, but to the best of the authors’ knowledge, no study has been conducted yet, in which gradient composition changes radially.

Design/methodology/approach

A powder metallurgy technique was used for the fabrication of Al-SiC-based, three-and five-layered functionally graded (FG) disk. The variation of volume fraction of reinforcement particles (SiC) in a disk changes radially. Finite element analysis has been performed to investigate stress distribution in a layered disk.

Findings

The microstructural investigation was carried out under an optical microscope and scanning electron microscopy integrated with EDS, confirming a uniform distribution of SiC in the matrix (Al). Interface microstructure indicates a successful fabrication of FG material because the transition is uniform in the graded layer without any development of crack or void at the interface. The grain size in the layers decreases with the addition of SiC particles. Additionally, the disk hardness increases as the SiC composition in the layer increases.

Practical implications

An FG disk can be used in a wide range of machinery, from power transmission assemblies to energy storage devices (e.g. flywheel, gears, rotors and disk brake).

Originality/value

The proposed powder metallurgy technique could be used in industries for the fabrication of simple to complicated geometries with FG properties.
Other customers' service failure and recovery encounters: a qualitative exploration
Authors: Gupta Niharika , Verma Harsh V.
Published: August 2022

Purpose

Service failure and recovery encounters are often witnessed by other customers, but little is known about how these encounters impacts other customers. With an aim to bridge this gap, the purpose of the paper is to explore why and how service recovery directed at a focal customer impacts other customers who are present in the same service environment.

Design/methodology/approach

The paper follows a qualitative research methodology. Purposive sampling was used to collect data from 30 customers through semi-structured face-to-face interviews. The data was analysed using thematic analysis.

Findings

Findings of the study show that service recovery directed at a focal customer has an impact on other customers' fairness judgments, emotions, service quality perceptions and behaviour. Other customers' behavioural reactions in response to observed service recovery are driven by two different motives: self-interest and moral obligation. Observing customers' cautious behaviour and (re)purchase behaviour are found to be primarily driven by self-interest, whereas their helping behaviour, punishment behaviour and word-of-mouth behaviour are found to be driven by moral obligation.

Research limitations/implications

This study findings contribute to theory development on “other-oriented” effects of service recovery and provides valuable insights for effective management of service failures in the shared service environment.

Originality/value

This is the first study, which qualitatively explores the “other customers” perspective of service recovery in the context of shared servicescape.
Social aspect versus service quality in trust formation toward mobile payment adoption: a case study of Indonesia
Authors: Lisana  , Handarkho Yonathan Dri
Published: August 2022

Purpose

This research aims to investigate the significant influence of social factors based on the social impact theory against service quality factors based on uncertainty avoidance dimension in determining user perception of trust toward mobile payment (MP) usage.

Design/methodology/approach

The theoretical model used was analyzed by adopting the structural equation modeling technique. Questionnaires were delivered to Indonesian customers as the target respondents using Google Forms, and finally, 659 valid responses were received.

Findings

Based on the direct effect analysis, service quality had more influence on the user trust perception than the social aspect. More specifically, Perceived Security was the most influential in increasing the level of user trust followed by Perceived Usefulness and Network Externalities.

Originality/value

This research presents a comprehensive investigation that applied a different perspective of the way social and service quality aspects develop user trust toward MP usage.
Impact of MD&A sentiment on corporate investment in developing economies: Chinese evidence
Authors: Fedorova Elena , Drogovoz Pavel , Nevredinov Alexandr , Kazinina Polina , Qitan Cai
Published: August 2022

Purpose

The goal of the study is to examine the effects of management discussion and analysis (MD&A) sentiment in public companies' annual reports on corporate investment incentives in developing economies.

Design/methodology/approach

The authors use sentiment analysis of MD&A texts based on Loughran and McDonald (2011) and combination of panel data regression, logit model and random forest. The text data consists of 3,511 annual reports of Chinese listed companies for the period from 2010 to 2019.

Findings

This paper provides empirical evidence of signaling theory that sentiment of annual reports and MD&A influences corporate decisions on both M&A and internal investments. The authors found that comparing to annual reports MD&A sentiment has more stable and significant explanatory and predictive power.

Practical implications

This paper confirms the importance of MD&A sentiment for corporate investment decision taking and provides practical techniques for analysts and researchers to study corporate investment incentives from the point of view of signaling theory.

Originality/value

The study aims to expand the domains of signaling theory and corporate investment valuation by including a broader range of data on companies' M&A and internal investments in developing economies. To explore the impact of MD&A sentiment on corporate investment, a state-of-the-art set of text mining and machine learning techniques is used. The authors' results confirm that MD&A has signaling effect and can get a positive market response. Furthermore, this study enhances the empirical evidence of overconfidence theory, i.e. optimistic management whose MD&A tend to positive overestimates the management's investments decision and also underestimate the potential risk to the firm.
Managerial Coase theorem: evidence from China
Authors: Gao Shaohui , He Yiming
Published: August 2022

Purpose

This paper aims to take a step in this direction and use the high dimensional fixed effects and quantile regression discontinuity design to test the managerial Coase theorem, which provides an institutional perspective for us to gauge the impact of private property rights on firm performance and the effect of management costs on intermediate inputs.

Design/methodology/approach

This study first uses high dimensional regression discontinuity designs to examine the impact of privatization on firm performance in China between 1998 and 2013.

Findings

Results indicate that privatization effects increase average outputs of the firm by around 10% given lower management costs, and management costs increase intermediate inputs by more than 50% points. Using data from annual surveys to test managerial Coase theorem, the authors show that management costs negatively affect the marginal effect of privatization on the average outputs of the firm. The positive impact on the investment in intermediate goods and services is larger in magnitude under higher management costs.

Originality/value

The authors develop the managerial Coase theorem. Today, given lower management costs, private property rights provide an incentive structure for a firm to maximize the value of the assets and expand the boundaries.
Supply chain network structure and firm's R&D investments: empirical evidence from Chinese manufacturing firms
Authors: Huang Heshu , Zhang Jiping , Yan Ji , Gong Yu , Wang Liukai
Published: August 2022

Purpose

The purpose of this research is to investigate the R&D investment (RDI) of manufacturing firms from the perspective of supply chain network, especially the effect of firms' supply chain network structures (network power and network cohesion) on its RDI, and further to explore the contingency conditions of this effect within the context of Chinese manufacturing supply chains.

Design/methodology/approach

The authors collect a large sample of Chinese manufacturing firms over the period 2014–2019 and construct a large-scale supply chain network, and finally obtain 2,390 firms from 20,483 observations. Ordinary least squares regression was adopted to analyse how supply chain network structures affect RDI in manufacturing firms.

Findings

It is surprising that firm's supply chain network structures have a negative effect on RDI. In addition, knowledge and technology intensity (KTI) positively moderate the relationship between network cohesion and RDI.

Originality/value

This study contributes to the innovation stream from the perspectives of supply chain network, and provides the empirical findings that the negative role of a firm's supply chain network structure on its RDI for the first time. The rationale for these negative effects is straightforward according to the social capital theory that manufacturing firms with a high level of social capital that are possibly to accept established patterns of thinking and behaviour, causing them to decrease the enthusiasm of RDI.
Disruptive human resource management technologies: a systematic literature review
Authors: Priyashantha K.G. , De Alwis A. Chamaru , Welmilla Indumathi
Published: August 2022

Purpose

The disruptive human resource management (HRM) technologies are now considered a significant facilitator to change and benefit the entire HRM landscape. This view needs to be further verified by reviewing the knowledge on the subject in the empirical research landscape. Thus, the study's objectives were to find (1) the current knowledge and (2) the areas where empirical research is lacking in disruptive HRM technologies.

Design/methodology/approach

The article is a literature review that was followed by the systematic literature review and the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The review considered 45 articles published during the 2008–2021 period extracted from the Scopus database, and bibliometric analysis was performed to achieve the research objectives.

Findings

The results found that scholarly attention has been given to electronic HRM (E-HRM) rather than the disruptive HRM technologies. The areas investigated include the determinants of intention, adoptions and use of E-HRM and the outcomes of E-HRM adoptions and use. These outcomes can be further divided into general outcomes and HRM outcomes.

Research limitations/implications

The findings reveal gaps in E-HRM research and disruptive HRM technologies remain untapped in the empirical research landscape. Hence, the study findings provide some implications for future research and applications.

Originality/value

The study found empirically proven determinants of E-HRM intention, adoptions and use and E-HRM adoptions and use outcomes. These were found in the studies conducted during the 2008–2021 period.
An empirical survey on prevalence and demographic differences in academic dishonesty among undergraduates from four public universities in China
Authors: Liu Xinjuan , Alias Noryati
Published: August 2022

Purpose

This empirical survey is conducted to investigate the prevalence rate of academic dishonesty (AD) in examinations and assignments among undergraduates. The study compared the difference in admitted behaviours of academic dishonesty between male and female students comprising second-year, third-year and fourth-year students from the discipline of business, engineering, information technology (IT) and education.

Design/methodology/approach

A cross-sectional study was utilized in this study and collected data via the online questionnaire. A total of 1,624 respondents participated from four public universities of four provinces in China Mainland.

Findings

The findings showed that the proportion of respondents from China participating in AD is between 15.4 and 51.7%. The findings showed that more than two-thirds of the respondents stated involved dishonesty in examinations and assignments at least once during the previous academic year. In addition, male and female undergraduates in second-year, third-year and fourth-year showed statistically significant differences in dishonest behaviours. Specifically, the male/senior students were more involved in dishonest behaviours than the females/sophomores.

Originality/value

Unlike previous studies, this study found that discipline in the Chinese context was not a significant demographic predictor of dishonesty. Although not significantly different, the respondents majoring in business reported a high engagement rate of dishonesty, followed by engineering and information technology undergraduates, but education undergraduates revealed the lowest engagement rate of dishonesty. The target integrity education should be imparted among male and senior students.
Submitting tentative solutions for platform feedback in crowdsourcing contests: breaking network closure with boundary spanning for team performance
Authors: Javadi Khasraghi Hanieh , Wang Xuan , Sun Jun , Javadi Khasraghi Bahar
Published: August 2022

Purpose

To obtain optimal deliverables, more and more crowdsourcing platforms allow contest teams to submit tentative solutions and update scores/rankings on public leaderboards. Such feedback-seeking behavior for progress benchmarking pertains to the team representation activity of boundary spanning. The literature on virtual team performance primarily focuses on team characteristics, among which network closure is generally considered a positive factor. This study further examines how boundary spanning helps mitigate the negative impact of network closure.

Design/methodology/approach

This study collected data of 9,793 teams in 246 contests from Kaggle.com. Negative binomial regression modeling and linear regression modeling are employed to investigate the relationships among network closure, boundary spanning and team performance in crowdsourcing contests.

Findings

Whereas network closure turns out to be a negative asset for virtual teams to seek platform feedback, boundary spanning mitigates its impact on team performance. On top of such a partial mediation, boundary spanning experience and previous contest performance serve as potential moderators.

Practical implications

The findings offer helpful implications for researchers and practitioners on how to break network closure and encourage boundary spanning with the establishment of facilitating structures in crowdsourcing contests.

Originality/value

The study advances the understanding of theoretical relationships among network closure, boundary spanning and team performance in crowdsourcing contests.