bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic characterization of cryptic species in the fungal pathogenHistoplasma
Authors: Sepúlveda Victoria E. , Rader Jonathan A. , Li Jingbaoyi (Janet) , Goldman William E. , Matute Daniel R.
Published: January 2024

Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease,Histoplasma,is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected byHistoplasmathrough inhalation of its spores (conidia) or mycelial particles. The fungi transitions into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. We have previously described thatHistoplasmais composed of at least five cryptic species that differ genetically, and assigned new names to the lineages. Here we evaluated multiple phenotypic characteristics of 12 strains from five phylogenetic species ofHistoplasmato identify phenotypic traits that differentiate between these species:H. capsulatum sensu stricto,H. ohiense,H. mississippiense,H. suramericanum, and an African lineage. We report diagnostic traits for two species. The other three species can be identified by a combination of traits. Our results suggest that 1) there are significant phenotypic differences among the cryptic species ofHistoplasma, and 2) that those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.

IMPORTANCE

Identifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, includingHistoplasma, and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics cannot be used for this purpose. In this study, we revise the taxonomic status of the four named species of the genusHistoplasma:H. capsulatum sensu stricto,H. ohiense,H. mississippiense, andH. suramericanumand propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study ofHistoplasma, but also for clinicians, as theHistoplasmaspecies could determine the outcome of disease and treatment needed.
Substrate Specificities of DDX1: A Human DEAD-box protein
Authors: Moore Anthony F. T. , Berhie Yepeth , Weislow Isaac S. , Koculi Eda
Published: January 2024

DDX1 is a human protein which belongs to the DEAD-box protein family of enzymes and is involved in various stages of RNA metabolism from transcription to decay. Many members of the DEAD-box family of enzymes use the energy of ATP binding and hydrolysis to perform their cellular functions. On the other hand, a few members of the DEAD-box family of enzymes bind and/or hydrolyze other nucleotides in addition to ATP. Furthermore, the ATPase activity of DEAD-box family members is stimulated differently by nucleic acids of various structures. The identity of the nucleotides that the DDX1 hydrolyzes and the structure of the nucleic acids upon which it acts in the cell remain largely unknown. Identifying the DDX1 protein’sin vitrosubstrates is important for deciphering the molecular roles of DDX1 in cells. Here we identify the nucleic acid sequences and structures supporting the nucleotide hydrolysis activity of DDX1 and its nucleotide specificity. Our data demonstrate that the DDX1 protein hydrolyzes only ATP and deoxy-ATP in the presence of RNA. The ATP hydrolysis activity of DDX1 is stimulated by multiple molecules: single-stranded RNA molecules as short as ten nucleotides, a blunt-ended double-stranded RNA molecule, a hybrid of a double-stranded DNA-RNA molecule, and a single-stranded DNA molecule. Under our experimental conditions, the single-stranded DNA molecule stimulates the ATPase activity of DDX1 at a significantly reduced extent when compared to the other investigated RNA constructs or the hybrid double-stranded DNA/RNA molecule.
A CPC-shelterin-BTR axis regulates mitotic telomere deprotection
Authors: Romero-Zamora Diana , Rogers Samuel , Low Ronnie Ren Jie , Robinson Andrew B. , Page Scott G. , Lane Blake J. E. , Lamm Noa , Ishikawa Fuyuki , Hayashi Makoto T. , Cesare Anthony J.
Published: January 2024

Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes telomere linearity and a localized ATM-dependent telomere DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, and super-resolution imaging, we found that mitotic arrest-dependent (MAD) telomere deprotection requires the combined activities of the Chromosome passenger complex (CPC) on shelterin, and the BLM-TOP3A-RMI1/2 (BTR) complex on t-loops. During mitotic arrest, the CPC component Aurora Kinase B (AURKB) phosphorylated both the TRF1 hinge and TRF2 basic domains. The former enhanced CPC and TRF1 interaction through the CPC Survivin subunit, while the latter promoted telomere linearity, telomere DDR activation dependent upon BTR double Holliday junction dissolution activity, and mitotic death. We identify that the TRF2 basic domain functions in mitosis-specific telomere protection and reveal TRF1 regulation over a physiological ATM-dependent telomere DDR. The data demonstrate that MAD telomere deprotection is a sophisticated active mechanism that exposes telomere ends to signal mitotic stress.
The glucocorticoid response element near the sphingosine-1-phopshate receptor 3 gene mitigates inflammatory processes and maladaptive behavior in females and stressed males
Authors: Corbett Brian F. , Arner Jay , Luz Sandra , Estela-Pro Valerie , Yan Jason , Osborne Brittany , Joannas Leonel , Henao-Mejia Jorge , Castro-Vildosola Jose , Hala Tamara , Bassing Craig , Harman Adele , Taylor Deanne , Bhatnagar Seema
Published: January 2024

It is well established that glucocorticoid receptors (GRs) bind DNA, regulate gene expression, reduce inflammatory processes, and modulate behavior. However, the precise loci bound by GRs that are necessary for these effects are not fully understood. Here, we deleted the GR binding site near the sphingosine-1-phospate receptor 3 gene using a CRISPR/Cas9 approach (S1PR3GR-/GR-rats). Defeated S1PR3GR-/GR-males displayed increased inflammatory markers and social anxiety-like behavior. Similar effects were observed in non-stressed females, indicating a greater dependence for GR-induced S1PR3 in females. Coherent neural activity between the locus coeruleus (LC) and medial prefrontal cortex (mPFC) was increased in S1PR3GR-/GR-males following 7 defeats. Chemogenetically inhibiting mPFC-projecting LC neurons during defeat increased subsequent social interaction in wild-type and S1PR3GR-/GR-males. Together, these findings demonstrate that GR-induced S1PR3 promotes resilience by mitigating stress-induced inflammatory processes and LC-mPFC coherence.

One Sentence Summary

Glucocorticoid receptor-induced expression of sphingosine-1- phosphate receptor 3 reduces social anxiety-like behavior by mitigating stress-induced inflammatory processes and coherent neural activity between the locus coeruleus and medial prefrontal cortex.
Taking identity-by-descent analysis into the wild: Estimating realized relatedness in free-ranging macaques
Authors: Freudiger Annika , Jovanovic Vladimir M. , Huang Yilei , Snyder-Mackler Noah , Conrad Donald F. , Miller Brian , Montague Michael J. , Westphal Hendrikje , Stadler Peter F. , Bley Stefanie , Horvath Julie E. , Brent Lauren J. N. , Platt Michael L. , Ruiz-Lambides Angelina , Tung Jenny , Nowick Katja , Ringbauer Harald , Widdig Anja
Published: January 2024

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by-descent (IBD) yield the most precise estimates of relatedness. Here, we leverage novel methods for estimating locus-specific IBD from low coverage whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4-6× coverage data from a rhesus macaque (Macaca mulatta) population with available long-term pedigree data, we show that we can call the number and length of IBD segments across the genome with high accuracy even at 0.5× coverage. The resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. They identify cryptic genetic relatives that are not represented in the pedigree and reveal elevated recombination rates in females relative to males, which allows us to discriminate maternal and paternal kin using genotype data alone. Our findings represent a breakthrough in the ability to understand the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.
ER-detect: a pipeline for robust detection of early evoked responses in BIDS-iEEG electrical stimulation data
Authors: van den Boom Max A. , Gregg Nicholas M. , Valencia Gabriela Ojeda , Lundstrom Brian N. , Miller Kai J. , van Blooijs Dorien , Huiskamp Geertjan J.M. , Leijten Frans S.S. , Worrell Gregory A. , Hermes Dora
Published: January 2024

Human brain connectivity can be measured in different ways. Intracranial EEG (iEEG) measurements during single pulse electrical stimulation provide a unique way to assess the spread of electrical information with millisecond precision. To provide a robust workflow to process these cortico-cortical evoked potential (CCEP) data and detect early evoked responses in a fully automated and reproducible fashion, we developed Early Response (ER)-detect. ER-detect is an open-source Python package and Docker application to preprocess BIDS structured iEEG data and detect early evoked CCEP responses. ER-detect can use three response detection methods, which were validated against 14 manually annotated CCEP datasets from two different sites by four independent raters. Results showed that ER-detect’s automated detection performed on par with the inter-rater reliability (Cohen’s Kappa of ∼0.6). Moreover, ER-detect was optimized for processing large CCEP datasets, to be used in conjunction with other connectomic investigations. ER-detect provides a highly efficient standardized workflow such that iEEG-BIDS data can be processed in a consistent manner and enhance the reproducibility of CCEP based connectivity results.
Genome-wide Polygenic Risk Scores Predict Risk of Glioma and Molecular Subtypes
Authors: Nakase Taishi , Guerra Geno , Ostrom Quinn T. , Ge Tian , Melin Beatrice , Wrensch Margaret , Wiencke John K. , Jenkins Robert B. , Eckel-Passow Jeanette E. ,   Glioma International Case-Control Study (GICC), Bondy Melissa L. , Francis Stephen S. , Kachuri Linda
Published: January 2024

Background

Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to find efficient ways of capturing genetic risk factors using available germline data.

Methods

We developed a novel PRS (PRS-CS) that uses continuous shrinkage priors to model the joint effects of over 1 million polymorphisms on disease risk and compared it to an approach (PRS-CT) that selects a limited set of independent variants that reach genome-wide significance (P<5×10-8). PRS models were trained using GWAS results stratified by histological (10,346 cases, 14,687 controls) and molecular subtype (2,632 cases, 2,445 controls), and validated in two independent cohorts.

Results

PRS-CS was consistently more predictive than PRS-CT across glioma subtypes with an average increase in explained variance (R2) of 21%. Improvements were particularly pronounced for glioblastoma tumors, with PRS-CS yielding larger effect sizes (odds ratio (OR)=1.93, P=2.0×10-54vs. OR=1.83, P=9.4×10-50) and higher explained variance (R2=2.82% vs. R2=2.56%). Individuals in the 95thpercentile of the PRS-CS distribution had a 3-fold higher lifetime absolute risk ofIDHmutant (0.63%) andIDHwildtype (0.76%) glioma relative to individuals with average PRS. PRS-CS also showed high classification accuracy forIDHmutation status among cases (AUC=0.895).

Conclusions

Our novel genome-wide PRS may improve the identification of high-risk individuals and help distinguish between prognostic glioma subtypes, increasing the potential clinical utility of germline genetics in glioma patient management.

IMPORTANCE OF THE STUDY

Inherited genetic variation is one of only a few risk factors known to contribute to gliomagenesis. We leverage the largest available collection of genome-wide association studies for glioma to show that a genome-wide PRS approach that models the joint effect of correlated variants across the genome yields improved prediction of glioma risk. Our novel PRS also improves the classification of cases according toIDHmutation status. Additionally, we provide refined estimates of individual genetic susceptibility and show that risk scores in the highest percentiles of the PRS distribution confer significant increases in relative and lifetime absolute risk. Taken together, our findings provide further evidence of the potential for germline genotyping to be used as a clinical biomarker in the assessment of personalized glioma risk and the non-invasive management of patients with newly diagnosed brain tumors.
Obesity shapes selection for driver mutations in cancer
Authors: Tang Cerise , Castillon Venise Jan , Waters Michele , Fong Chris , Park Tricia , Boscenco Sonia , Kim Susie , Schultz Nikolaus , Ostrovnaya Irina , Gusev Alexander , Jee Justin , Reznik Ed
Published: January 2024

Obesity is a leading risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. Here, we examined the relationship between obesity and tumor genotype in two large clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma, and cancers of unknown primary, independent of clinical covariates and genetic ancestry. Obesity is therefore a putative driver of etiologic heterogeneity across cancers.
Generalizability in real-world trials
Authors: Näher Anatol-Fiete , Kopka Marvin , Balzer Felix , Schulte-Althoff Matthias
Published: January 2024

Real-world evidence (RWE) trials have a key advantage over conventional randomized controlled trials (RCTs) due to their possibly higher external validity. This allows for better generalizability of results to larger populations, which is essential for evidence-based decision making in clinical medicine, pharmacoepidemiology, and health policy. Random sampling of RWE trial participants is regarded the gold standard for generalizability. Additionally, the use of sample correction procedures can increase the generalizability of trial results, even when using non-randomly sampled real-world data (RWD). This study presents descriptive evidence on the extent to which the design of currently planned or already conducted RWD/E trials takes sampling into account. It also examines whether random sampling or procedures for correcting non-random samples are considered. Based on text-mining of publicly available metadata provided during registrations of RWD/E trials onclinicaltrials.gov, EU-PAS, and the OSF-RWE registry, it is shown that the share of RWD/E trial registrations with information on sampling increased from 65.27% in 2002 to 97.43% in 2022, with a corresponding increase from 14.79% to 28.30% for trials with random samples. For RWD/E trials with non-random samples, there is an increase from 0.00% to 0.22% of trials in which sample correction procedures are used. We conclude that the potential benefits of RWD in terms of generalizing trial results are not yet being fully realized.
Multimorbidity in Older Adults with Depression Study (MODS) (Behavioural Activation to improve physical and mental functioning among older people with multiple long-term conditions): Protocol for a fully powered randomised controlled trial
Authors: Ryde Eloise , Hollingsworth Kelly , Littlewood Elizabeth , Atha Lucy , Bailey Della , Baker Heather , Bosanquet Katharine , Shearsmith Leanne , Chew-Graham Carolyn A. , McMillan Dean , Baird Kalpita , Coventry Peter , Crosland Suzanne , Fairhurst Caroline , Wang Han-I , Burke Lauren , Heeley Janine , Hewitt Catherine , Clegg Andrew , Gentry Tom , Hill Andrew , Lovell Karina , Dexter-Smith Sarah , Traviss-Turner Gemma , Webster Judith , Agnew Elizabeth , Stevens Heidi , Webb Katie , Gilbody Simon , Ekers David
Published: January 2024

Introduction

Older adults (65 years or over) and those with long-term health conditions (LTCs), represent a ‘high risk’ group for depression, with a risk two-to-three times the general population. This can lead to poorer quality of life and be costly to health and social care services. In the Multimorbidity in Older Adults with Depression Study (MODS) we will test whether a brief psychological intervention (Behavioural Activation), helps to improve physical/mental functioning in this group compared to treatment as usual.

Methods

We will conduct a two-arm, parallel-group randomised controlled trial, to evaluate the clinical and cost-effectiveness of the MODS intervention. Participants will be recruited via general practices across England. To be included, participants must be aged 65 years or over, with two or more LTCs and either sub-threshold depression or major depression. Randomisation will be simple 1:1. Intervention participants will receive up to eight sessions delivered by MODS support workers, supported by a self-help booklet. Control participants will receive usual care.

A process evaluation will be undertaken to evaluate the processes and mechanisms underpinning intervention delivery, and to inform the development of an implementation framework. Semi-structured interviews will be conducted with intervention participants, participant’s caregivers/supportive others, and health and social care professionals. Focus groups and semi-structured interviews will be conducted with MODS support workers. Outcome data will be collected at four, eight, and twelve-months post-randomisation. The primary outcome is self-reported quality of life and functioning at the four-month follow up. Secondary outcomes include depression, anxiety, physical functioning, loneliness, social isolation, chronic pain, health related quality of life, and health services use.

Discussion

This study builds on our previous work and will evaluate a brief psychological intervention to improve physical and mental health functioning for older adults with multiple long-term conditions.

Trial Registration

ClinicalTrials.Gov IdentifierISRCTN44184899, registered on 11thAugust 2022.
Gallein and isoniazid act synergistically to attenuateMycobacterium tuberculosisgrowth in human macrophages
Authors: Rijal Ramesh , Gomer Richard H.
Published: January 2024

Mycobacterium tuberculosis(Mtb), the bacterium that causes tuberculosis (TB), can be difficult to treat because of drug resistance. Increased intracellular polyphosphate (polyP) inMtbenhances resistance to antibiotics, and capsular polyP inNeisseria gonorrhoeaepotentiates resistance to antimicrobials. The mechanism by which bacteria utilize polyP to adapt to antimicrobial pressure is not known. In this study, we found thatMtbadapts to the TB frontline antibiotic isoniazid (INH) by enhancing the accumulation of cellular, extracellular, and cell surface polyP. Gallein, a broad-spectrum inhibitor of the polyphosphate kinase that synthesizes polyP, prevents this INH-induced increase in extracellular and cell surface polyP levels. Gallein and INH work synergistically to attenuateMtb’s ability to grow inin vitroculture and within human macrophages.Mtbwhen exposed to INH, and in the presence of INH, gallein inhibits cell envelope formation in most but not allMtbcells. Metabolomics indicated that INH or gallein have a modest impact on levels ofMtbmetabolites, but when used in combination, they significantly reduce levels of metabolites involved in cell envelope synthesis and amino acid, carbohydrate, and nucleoside metabolism, revealing a synergistic effect. These data suggest that gallein represents a promising avenue to potentiate the treatment of TB.

Author summary

Mycobacterium tuberculosis(Mtb) is the causative agent of tuberculosis (TB), which is responsible for more deaths than any other infectious disease. The alarming prevalence of drug-resistantMtbstrains has further exacerbated this global health crisis. Some pathogenic bacteria such asMtbappear to increase levels of polyphosphate as a defense against antibiotics. We found that gallein, a small molecule inhibitor of bacterial polyphosphate kinases, strongly potentiates the ability of the frontline anti-tuberculosis drug isoniazid to inhibit the growth ofMtbboth alone and in human macrophages. This has unveiled vulnerabilities inMtbthat could be strategically leveraged to reverse INH resistance.
Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics
Authors: Conca Dario Valter , Bano Fouzia , Wirén Julius von , Scherrer Lauriane , Svirelis Justas , Thorsteinsson Konrad , Dahlin Andreas , Bally Marta
Published: January 2024

The worldwide spread of SARS-CoV-2 has been characterised by the emergence of several variants of concern (VOCs) presenting an increasing number of mutations in the viral genome. The spike glycoprotein, responsible for engaging the viral receptor ACE2, exhibits the highest density of mutations, suggesting an ongoing evolution to optimize viral entry. However, previous studies focussed on isolated molecular interactions, neglecting the intricate composition of the plasma membrane and the interplay between viral attachment factors. Our study explores the role of avidity and of the complexity of the plasma membrane composition in modulating the virus-host binding kinetics during the early stages of viral entry for the original Wuhan strain and three VOCs: Omicron BA.1, Delta, and Alpha. We employ fluorescent liposomes decorated with spike from several VOCs as virion mimics in single-particle tracking studies on native supported lipid bilayers derived from pulmonary Calu-3 cells. Our findings reveal an increase in the affinity of the multivalent bond to the cell surface for Omicron driven by an increased association rate. We show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed on cells’ plasma membrane, plays a central role in modulating the interaction with the cell surface and we observe a shift in its role from screening the interaction with ACE2 in early VOCs to an important binding factor for Omicron. This is caused by a ∼10-fold increase in Omicron’s affinity to HS compared to the original Wuhan strain, as shown using atomic force microscopy-based single-molecule force spectroscopy. Our results show the importance of coreceptors, particularly HS, and membrane complexity in the modulation of the attachment in SARS-CoV-2 VOCs. We highlight a transition in the variants’ attachment strategy towards the use of HS as an initial docking site, which likely plays a role in shaping Omicron’s tropism towards infection of the upper airways, milder symptoms, and higher transmissibility.
Enhanced feature matching in single-cell proteomics characterizes response to IFN-γ and reveals co-existence of different cell states
Authors: Krull Karl K. , Ali Syed A. , Krijgsveld Jeroen
Published: January 2024

Proteome analysis by data-independent acquisition (DIA) has become a powerful approach to obtain deep proteome coverage, and has gained recent traction for label-free analysis of single cells. However, optimal experimental design for DIA-based single-cell proteomics has not been fully explored, and performance metrics of subsequent data analysis tools remain to be evaluated. Therefore, we here present DIA-ME, a data analysis strategy that exploits the co-analysis of low-input samples with a so-called matching enhancer (ME) of higher input, to increase sensitivity, proteome coverage, and data completeness. We evaluate the matching specificity of DIA-ME by a two-proteome model, and demonstrate that false discovery and false transfer are maintained at low levels when using DIA-NN software, while preserving quantification accuracy. We apply DIA-ME to investigate the proteome response of U-2 OS cells to interferon gamma (IFN-γ) in single cells, and recapitulate the time-resolved induction of IFN-γ response proteins as observed in bulk material. Moreover, we observe co- and anti-correlating patterns of protein expression within the same cell, indicating mutually exclusive protein modules and the co-existence of different cell states. Collectively our data show that DIA-ME is a powerful, scalable, and easy-to- implement strategy for single-cell proteomics.
Stratifying macrophages based on their infectious burden identifies novel host targets for intervention during Crohn’s disease associated adherent-invasiveEscherichia coliinfection
Authors: Li Xiang , Cole John , Vaughan Diane , Xiao Yinbo , Walker Daniel , Wall Daniel M.
Published: January 2024

Bacterial infection is a dynamic process resulting in a heterogenous population of infected and uninfected cells. These cells respond differently based on their bacterial load and duration of infection. In the case of infection of macrophages with Crohn’s disease (CD) associated adherent-invasiveEscherichia coli(AIEC), understanding the drivers of pathogen success may allow targeting of cells where AIEC replicate to high levels. Here we show that stratifying immune cells based on their bacterial load identifies novel pathways and therapeutic targets not previously associated with AIEC when using a traditional homogeneous infected population approach. Using flow cytometry-based cell sorting we stratified cells into those with low or high intracellular pathogen loads, or those which were bystanders to infection. Immune cells transcriptomics revealed a diverse response to the varying levels of infection while pathway analysis identified novel intervention targets that were directly related to increasing intracellular AIEC numbers. Chemical inhibition of identified targets reduced AIEC intracellular replication or inhibited secretion of tumour necrosis factor alpha (TNFα), a key cytokine associated with AIEC infection. Our results have identified new avenues of intervention in AIEC infection that may also be applicable to CD through the repurposing of already available inhibitors. Additionally, they highlight the applicability of immune cell stratification post-infection as an effective approach for the study of microbial pathogens.
SARS-CoV-2 papain-like protease activates nociceptors to drive sneeze and pain
Authors: Mali Sonali S. , Silva Ricardo , Gong Zhongyan , Cronce Michael , Vo Uyen , Vuong Cliff , Moayedi Yalda , Cox Jeffery S. , Bautista Diana M.
Published: January 2024

SARS-CoV-2, the virus responsible for COVID-19, triggers symptoms such as sneezing, aches and pain.1These symptoms are mediated by a subset of sensory neurons, known as nociceptors, that detect noxious stimuli, densely innervate the airway epithelium, and interact with airway resident epithelial and immune cells.2–6However, the mechanisms by which viral infection activates these neurons to trigger pain and airway reflexes are unknown. Here, we show that the coronavirus papain-like protease (PLpro) directly activates airway-innervating trigeminal and vagal nociceptors in mice and human iPSC-derived nociceptors. PLpro elicits sneezing and acute pain in mice and triggers the release of neuropeptide calcitonin gene-related peptide (CGRP) from airway afferents. We find that PLpro-induced sneeze and pain requires the host TRPA1 ion channel that has been previously demonstrated to mediate pain, cough, and airway inflammation.7–9Our findings are the first demonstration of a viral product that directly activates sensory neurons to trigger pain and airway reflexes and highlight a new role for PLpro and nociceptors in COVID-19.
The deep-sea ecosystem engineerGeodia barretti(Porifera, Demospongiae) maintains basic physiological functions under simulated future ocean pH and temperature conditions
Authors: Wurz Erik , Ulvatn Tone , Kooistra Tjitske , Strauss Florian , Rapp Hans Tore , Goeij Jasper M. de , Osinga Ronald
Published: January 2024

Global ocean warming and acidification will alter the physicochemical conditions in the deep North-Atlantic Ocean. Here, extensive sponge grounds, often dominated by the demosponge speciesGeodia barretti, provide three-dimensional structure, habitat and significantly contribute to benthic-pelagic coupling and nutrient cycling processes in the deep sea. It is unknown ifG. barrettiremains physiologically functional under the future physicochemical properties of an Anthropocene ocean. In this study, individuals ofG. barretticollected from 300 m water depth in the Barents Sea, were exposed to four treatments resembling future ocean conditions (no treatment, 4 °C increase in seawater temperature, decrease of seawater pH by 0.3, and a combination of the high temperature, low pH). Over the course of 39 weeks, oxygen consumption, dissolved inorganic nutrient fluxes, and bacterioplankton clearance rates were measured as indicators of metabolic activity. We found that all indicators within each sponge individual and per treatment were highly variable over time and no effect of manipulated seawater treatments on these parameters could be demonstrated. Oxygen consumption rates in all groups closely followed a seasonal pattern, potentially caused by (a)biotic cues in the seawater flowing through the experimental aquaria. While similar metabolic rates across all treatments suggest thatG. barrettiphysiologically coped with simulated future ocean conditions, observed tissue necrosis in experimental animals might indicate that the response of the complex, high microbialG. barrettisponge (i.e., sponge host and microbial symbionts) to future ocean conditions may not be reflected in basic physiological processes.
Large Neutrino Secret Interactions Have a Small Impact on Supernovae
Authors: Fiorillo Damiano F. G. , Raffelt Georg G. , Vitagliano Edoardo
Published: January 2024

When hypothetical neutrino secret interactions (νSI) are large, they form a fluid in a supernova (SN) core, flow out with sonic speed, and stream away as a fireball. For the first time, we tackle the complete dynamical problem and solve all steps, systematically using relativistic hydrodynamics. The impact on SN physics and the neutrino signal is remarkably small. For complete thermalization within the fireball, the observable spectrum changes in a way that is independent of the coupling strength. One potentially large effect beyond our study is quick deleptonization if νSI violate lepton number. By present evidence, however, SN physics leaves open a large region in parameter space, where laboratory searches and future high-energy neutrino telescopes will probe νSI.

Published by the American Physical Society
2024
The influence of country-of-origin on consumers' purchase intention: a study of the Chinese smartphone market
Authors: Blanco-Encomienda Francisco Javier , Chen Shuo , Molina-Muñoz David
Published: January 2024

Purpose

Due to the intense rivalry in the smartphone market, manufacturers of mobile phones are becoming increasingly interested in knowing the factors that influence consumers' purchase intention. This paper aims to examine the effect of country-of-origin image, brand image and attitude towards the brand on the purchase intention of smartphone users.

Design/methodology/approach

An empirical study was performed based on the information gathered from smartphone users. The structural equation modeling (SEM) technique was applied to examine the hypotheses.

Findings

The authors found that brand image and attitude towards the brand significantly influence consumer purchase intention. Additionally, there is an indirect effect even when the nation of origin image does not directly influence the consumer's purchase intention. Indeed, brand image and attitude towards the brand act as a mediator between the country-of-origin image and purchase intention.

Originality/value

This study presents a conceptual model on the impact of country-of-origin image on the propensity of consumers to buy smartphones in a field where little research has been done. The investigation offers a consumer-focused analysis regarding the country-of-origin image. This suggests a significant shift from the current strategy, which is frequently centered on the viewpoint of the companies.
Loan loss provisions and income smoothing in banks: the role of trade openness and IFRS in BRICS
Authors: Biswas Sarit , Bhattacharya Sharad Nath , Jin Justin Y. , Bhattacharya Mousumi , Sadarangani Pradip H.
Published: January 2024

Purpose

This paper empirically investigates whether trade openness (TO) in Brazil, Russia, India, China and South Africa (BRICS) countries affects how banks might employ loan loss provisions (LLPs) to smooth out their earnings and how adopting the International Financial Reporting Standards (IFRS) can mitigate it.

Design/methodology/approach

The analysis includes 78 commercial banks from five BRICS nations and spans 2014 through 2020. To test these hypotheses, the authors utilized a fixed-effect and two-step system panel generalized methods of moments (GMM) estimator.

Findings

TO positively affects income smoothing (earnings management) across BRICS commercial banks. The effect is clearer in banks that make financial reports under the IFRS. Path analysis reveals that the effect of TO is driven by nonperforming loans (NPLs). Additionally, the IFRS restricts earnings management in the BRICS banking sector when a better institutional environment is present. The authors found that accounting rules (IFRS) and enforcement (better institutional settings) interact to enhance earnings’ quality.

Practical implications

The relationship between TO and bank earnings management practices is important for understanding the complex interplay between trade and finance and ensuring financial stability, investor confidence and regulatory compliance. This study recommends better regulations and governance mechanisms for financial reports in emerging nations like BRICS. Additionally, macro-prudential regulators and banking supervisors should work closely to ensure transparent TO decisions with improved discipline, institutional quality and regulatory support to enhance bank stability.

Originality/value

The study finds evidence of bank income smoothing in the BRICS and introduces TO as a determinant. It also identifies the evolving role of IFRS in the presence of higher institutional quality and TO, thereby expanding the financial reporting literature.
Compliance is the armour for lending institution: a case study related to agri-finance
Authors: Sachdeva Geeta
Published: January 2024

Learning outcomes

The case study will help to learn about the importance of pre-sanction precautionary measures before lending to self-help groups (SHGs), to learn about the potential lapses and errors while sanctioning SHG finance and to learn about the importance of bank’s guidelines and compliance before sanctioning loans.

Case overview/synopsis

This case study details the tenure of Seema in a rural branch of Safe Bank of India located in Haryana which she joined as a manager in the year 2016. She overachieved the target given by the district collector office, and going by the tide, she kept her reliance on the references provided by non-government organization (NGO) without complying the bank’s instructions. She committed errors while sanctioning the loans, which led towards the upsurge of non-performing assets of the branch. Later on, after investigation it was discovered that she did not follow fundamental bank’s instructions. In wake of those lapses and errors, how she could have avoided those lapses and secure the public money? What were the most important documents while granting agriculture finance and what due diligence she should have taken? How did she treat calls from the government departments? Was she right in trusting the suggestions of the NGO?

Complexity academic level

This case study caters to students of various streams, namely, management, business administration and law, and can be targeted at both undergraduate and postgraduate students. It could be suitable for several types of courses and students. Furthermore, this case study can also be targeted for various training programmes for bank employees and employees of various lending institutions engaged in agriculture finance and credit linkage programmes.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 1: Accounting and finance.
A new grey relational analysis model of cross-sequences
Authors: Liu Sifeng , Lu Ningning , Shang Zhongju , Rathnayaka R.M. Kapila Tharanga
Published: January 2024

Purpose

The purpose of this paper is to explore a new approach to solve the problem of positive and negative offset in the calculation process of integral elements, then propose a series of new grey relational degree model for cross sequences.

Design/methodology/approach

The definitions of cross sequences and area elements have been proposed at first. Then the concept of difference degree between sequences has been put forward. Based on the definition of difference degree between sequences, various modified grey relational degree models for cross sequences have been proposed to solve the measurement problem of cross sequence correlation relationships.

Findings

(1) The new definition of cross sequences; (2) The area element; (3) Various modified grey relational degree models for cross sequences based on the definition of difference degree between sequences.

Practical implications

The grey relational analysis model of cross sequences is a difficult problem in grey relational analysis. The new model proposed in this article can effectively avoid the calculation deviation of grey relational analysis model for cross sequences, and reasonably measure the correlation between cross sequences. The new model was used to analyse the food consumer price index in Shaanxi Province, clarifying the relationship between different types of food consumer price indices, some interesting results that are not completely consistent with general economic theory were obtained.

Originality/value

The new definition of cross sequences, the area element and various modified grey relational degree models for cross sequences were proposed.
How best to advertise low-fit brand extensions: a construal level theory perspective
Authors: Saeed Muhammad Rashid , Lee Richard , Lockshin Larry , Bellman Steven , Yang Song , Cohen Justin
Published: January 2024

Purpose

Low-fit brand extensions offer several potential benefits, yet their success is challenging. Building on construal level theory, this study aims to investigate how different advertising appeals can improve the evaluations of low-fit brand extensions through two different processes (cognitive and affective).

Design/methodology/approach

Two experiments were conducted with US consumers. Study 1 used a 2 (extension fit: high, low) × 2 (ad appeal: abstract, concrete) between-subjects design. Study 2 applied a 2 (brand associations: promotion, prevention) × 2 (ad appeal: promotion, prevention) between-subjects design. Multivariate analyses and follow-up means comparisons were used to analyse data.

Findings

Study 1 found that an abstract ad appeal is more effective for promoting low-fit brand extension because it improves the perception of fit. Study 2 showed promotion vs prevention ad appeals lead to better evaluation of low-fit brand extensions when matched with parent brand associations (promotion vs prevention) in terms of construal level. This matching effect is underpinned by processing fluency.

Research limitations/implications

Ad appeals can influence low-fit brand extension evaluation by influencing the perception of fit (cognitive process) or processing fluency (affective process). Future research could consider different ad appeals and other construal related factors to generalise these findings.

Practical implications

Marketers can design different ad appeals to effectively advertise low-fit brand extensions. These findings can guide managers in the development of effective advertising strategies.

Originality/value

This research offers a new perspective on how ad appeals can enhance low-fit brand extension evaluation.
Commentary: developing a deeper understanding of resilience in service contexts
Authors: Good Valerie
Published: January 2024

Purpose

This paper aims to comment on resilience research within the context of frontline employees in sales and services marketing.

Design/methodology/approach

This commentary is a reflection based on my research, extant academic and managerial literature and personal perspectives.

Findings

Research findings show resilience is associated with increased employee effort and reduced turnover intentions in customer-facing roles. In addition, resilience can change over time and is not just a trait the employee is born with (or not). Hence, managers can cultivate resilience in employees.

Practical implications

Resilience cannot be purchased. Instead, managers can inspire resilience in frontline employees by developing their feelings of self-efficacy on the job, a sense of belongingness to the organization and peers and a sense of purpose and relatedness to customers.

Social implications

Resilience is not merely perseverance or grit; it is overcoming adversity and bouncing back to become better in the process. Thus, resilience is an important construct to study, particularly in customer-facing roles.

Originality/value

This commentary offers a unique approach to understanding resilience, its outcomes and its antecedents in customer-facing roles.
B2B collaborative economy: a joint sphere perspective
Authors: Corsaro Daniela , Murtarelli Grazia
Published: January 2024

Purpose

Scholars have affirmed that a conceptualization of value co-creation in business relationships should reflect the nature and characteristics of interactional processes that occur in use. The advent of sales and marketing technologies, however, is changing the nature and dynamics of interactions. New trends in digitalization have played a significant role in emphasizing and facilitating the occurrence of business-to- business (B2B) collaborative or sharing economy. The B2B sharing economy and value co-creation are closely intertwined, as businesses harness the power of shared resources and collaboration to generate value in diverse ways. This study highlights the importance of going beyond value co-creation in studying B2B collaborative economy, unpacking the interconnected value processes that influence value co-creation. It also aims at showing the activities that characterize multiple joint value spheres among actors.

Design/methodology/approach

The study consists of 49 qualitative interviews with managers operating in different industries.

Findings

The paper shows that when considering digital B2B contexts, five joint value spheres in business relationships should be considered: a value co-creation, a value appropriation, a value communication, a value measurement and a value representation sphere. Each one is characterized by specific activities that are relevant from a managerial point of view.

Originality/value

This study highlights that value co-creation has often been over stressed when discussing business interactions, also with the advent of new technologies. Rather, this study offers a more comprehensive view of value co-creation that includes different value processes occurring in joint value spheres. These further processes are relevant because failure and success in business relationships within the B2B sharing economy are often dependent from activities outside the value co-creation process, which strongly affect it. Such knowledge will also open up new research venues and opportunities to better contribute to the practice of value management in business relationships.
The role of leadership in organizational learning in multinational companies
Authors: Hekneby Torbjørn , Olsen Trude Høgvold
Published: January 2024

Purpose

This paper aims to conceptualize the role of leadership in organizational learning processes in multinational companies (MNCs). The authors present a model describing how managers in an MNC facilitated transitions between sub-processes of organizational learning at several organizational levels.

Design/methodology/approach

The authors collected data from the plants of a global process company in Norway, Brazil and China. Observation, in-depth interviews and archival material enabled one to reconstruct the organizational learning process over a period of 30 years as the company developed its own tailor-made improvement programme.

Findings

Based on the data, the authors describe the role of leadership in linking the sub-processes of organizational learning as orchestration, sponsoring and persistence. Orchestration included creating faith and optimism and designing the organization to allow close cooperation between operators and managers in the sub-process of experimenting. This eased transferring and institutionalizing in the global organization. Sponsoring included structural changes to support transferring and the demonstration of dedication to improvement programme values. These factors were important for institutionalizing. Persistence involved the continuous focus on adjustment of the improvement programme, which then facilitated further experimenting.

Originality/value

Firstly, this study suggests that activities and decisions in one sub-process have important implications for the following sub-processes. Secondly, this study indicates that leaders’ role in facilitating the transitions between sub-processes extend beyond their individual traits and behaviour, which previous research had focused on, and includes decisions concerning organizational structure and culture that help link social and organizational learning.