bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological factors that drive microbial communities in culturally diverse fermented foods
Authors: Gautam Arya , Poopalarajah Rahgavi , Ahmad Anique R , Rana Bimarsh , Denekew Tsedenia W , Anh Nakyeong , Utenova Lina , Kunwar Yadu Sudan , Bhandari Nitin N , Jha Aashish R
Published: August 2024

Fermented foods are increasingly recognized for their health benefits. Historically, cultures worldwide have relied on fermentation to preserve foods and enhance their digestibility, flavor, aromas, and taste. Despite the abundance of global diversity of fermented foods, the microbial communities in traditionally fermented non-European foods remain largely understudied. Here, we characterized the bacterial and fungal communities in 90 plant and animal based fermented foods from Nepal, South Korea, Ethiopia, and Kazakhstan, all traditionally prepared for household consumption. Our results reveal that these foods host diverse and intricately interconnected ecosystems of bacteria and fungi. Beyond the well-known fermenters such as lactic acid bacteria (LABs), Bacillales, and yeasts (Saccharomycetales), these foods contain additional microbes whose roles in fermentation are not well understood. While the microbial compositions of fermented foods vary by geography and preparation methods, the type of food substrate has the most significant effect on differentiating bacterial communities. Vegetable-based ferments harbor bacterial communities consisting primarily of LABs and potential pathways associated with carbohydrates degradation. Contrastingly, legumes and animal-based fermented foods are enriched with Bacillales and protein and lipid degradation pathways. Moreover, the microbial interactions, characterized via bacteria-bacteria and bacteria-fungi co-occurrence networks, differ significantly across traditionally fermented plants, legumes, and dairy products, indicating that microbial ecosystems vary between traditional fermented foods derived from different substrates. Our findings highlight the underexplored diversity of microbial communities in traditional fermented foods and underscore the need to understand the entire microbial communities present in these foods and their functions when evaluating their effect on nutrition and health.
Conserved RNA-binding protein interactions mediate syntologous lncRNA functions
Authors: Sabaté-Cadenas Xavier , Lavalou Perrine , Ross Caroline Jane , Chen Lee , Zielinski Dina , Vacher Sophie , Ledevin Mireille , Larcher Thibaut , Petitjean Matthieu , Damy Louise , Servant Nicolas , Bièche Ivan , Ulitsky Igor , Shkumatava Alena
Published: August 2024

Syntologous long noncoding RNAs (lncRNAs) are loci with conserved genomic positions that often show little or no sequence similarity. Despite diverging primary sequences, lncRNA syntologs from distant species can carry out similar functions. However, determinants underlying conserved functions of syntologous lncRNA transcripts with no sequence similarity remain unknown. UsingCASC15and melanoma formation as a paradigm for fast evolving lncRNAs and their functions, we found that human and zebrafishCASC15syntologs with no detectable sequence similarity retained their function across 450 million years of evolution. Similar to thecasc15-deficient zebrafish,CASC15-mutant human melanoma cells show increased cell migration. Expression of humanCASC15in zebrafish rescues loss ofcasc15function by attenuating melanoma formation. This conserved function is supported by a set of RNA-binding proteins, interacting with both zebrafish and humanCASC15transcripts. Together, our findings demonstrate that conserved RNA-protein interactions can define functions of rapidly evolving lncRNA transcripts.
Exploring the diversity of anti-defense systems across prokaryotes, phages, and mobile genetic elements
Authors: Tesson Florian , Huiting Erin , Wei Linlin , Ren Jie , Johnson Matthew C. , Planel Remi , Cury Jean , Feng Yue , Bondy-Denomy Joseph , Bernheim Aude
Published: August 2024

The co-evolution of prokaryotes, phages, and mobile genetic elements (MGEs) over the past billions of years has driven the emergence and diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences, and are typically small, creating a challenge to detect anti-defense homologs across the prokaryotic genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired genome or MGE. Here, we developed "AntiDefenseFinder" - a free open-source tool and web service that detects 156 anti-defense systems (of one or more proteins) in any genomic sequence. Using this dataset, we identified 47,981 anti-defense systems distributed across prokaryotes, phage, and MGEs. We found that some genes co-localize in "anti-defense islands", including E. coli T4 and Lambda phages, although many are standalone. Out of the 112 systems detected in bacteria, 100 systems localize only or preferentially in prophages, plasmids, phage satellites, integrons, and integrative and conjugative elements. However, over 80% of anti-Pycsar protein 1 (Apyc1) resides in non-mobile regions of bacteria. Evolutionary and functional analyses revealed that Apyc1 likely originated in bacteria to regulate cNMP signaling, but was co-opted multiple times by phages to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions, and a deeper understanding of host-pathogen arms race.
Spinal Cord Injury Enhances Lung Inflammation and Exacerbates Immune Response After Acute Lung Injury
Authors: Berk Bradford C , Pereira Amanda , Vizcarra Velia Sofia , Proschel Christoph , Hsu Chia George
Published: August 2024

The severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between disrupted sympathetic regulation and splenocyte apoptosis in high thoracic SCI, leading to pulmonary dysfunction. The aim of this study was to investigate whether mice with low-level SCI exhibit increased susceptibility to acute lung injury by eliciting systemic inflammatory responses that operate independently of the sympathetic nervous system. Here, we employed T9 contusion SCI and exposed mice to aerosolized lipopolysaccharide (LPS) to simulate lung inflammation associated with acute respiratory distress syndrome (ARDS). Twenty-four hours post-LPS exposure, lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed. LPS markedly induced proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in SCI mice compared to controls, indicating an exaggerated inflammatory response. Infiltration of Ly6G/C positive neutrophils and macrophages was significantly higher in SCI mice lungs post-LPS exposure. Interestingly, spleen size and weight did not differ between control and SCI mice, suggesting that T9 SCI alone does not cause spleen atrophy. Notably, bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS. This study demonstrated an increase in lung inflammation and immune responses subsequent to low-level T9 SCI, underscoring the widespread influence of systemic inflammation post-SCI, especially pronounced in specific organs like the lungs.
Ultra-Sensitive Detection of Transposon Insertions Across Multiple Families by Transposable Element Display Sequencing
Authors: Vendrell-Mir Pol , Leduque Basile , Quadrana Leandro
Published: August 2024

Mobilization of transposable elements (TEs) can generate large effect mutations. However, because new TE insertions are challenging to detect and transposition is typically rare, the actual rate and landscape of new insertions remains unexplored for most TEs. Here, we introduce a TE display sequencing approach that leverages target amplification of TE extremities to detect non-reference TE insertions with high sensitivity and specificity. By implementing this approach on serial dilutions of genomic DNA from A. thaliana lines carrying different repertoires of new TE insertions, we show that the method can detect TE insertions that are present at frequencies as low as 1:250 000 within a DNA sample. In addition, TE display sequencing can be multiplexed to simultaneously detect insertions for distinct TE families, including both retrotransposons and DNA transposons, increasing its versatility and cost-effectiveness to investigate complex mobilomes. Importantly, when combined with nanopore sequencing, this approach enables the identification of insertions using long-reads and achieves a turn around time from DNA extraction to insertion identification of less than 24h, significantly reducing the time-to-answer. Analysis of TE insertions in large populations of A. thaliana plants undergoing a transposition burst demonstrate the power of the multiplex TE display sequencing to assess the rates and allele frequencies of heritable insertions, enabling its implementation to study large-scale evolve and resequence experiments. Furthermore, we found that ~6% of de novo TE insertions show recurrent allele frequency changes consistent with either positive or negative selection. We conclude that TE display sequencing is an ultra-sensitive, specific, quick, and cost-effective approach to investigate the rate and landscape of new insertions for multiple TEs in large scale population experiments. We provide a step-by-step experimental protocol as well as ready-to-use bioinformatic pipelines, ensuring straightforward implementation of the method.
Ex vivo Model of Functioning Human Lymph Node Reveals Pivotal Role for Innate Lymphoid Cells and Stromal Populations in Response to Vaccine Adjuvant
Authors: Fergusson Joannah , Siu Jacqueline , Gupta Nitya , Nee Eloise , Reinke Soren , Stroebel Tamara , Bhalla Ananya , Kandage Shyami , Courant Thomas , Hill Sarah , Attar Moustafa , Gordon-Weeks Alex , Coles Mark , Dendrou Calliope , Milicic Anita
Published: August 2024

Immunological processes that underpin the administration of therapeutics and vaccines are poorly defined due to a lack of models which faithfully recapitulate human immune responses. Inbred mice lack the diversity inherent to people, while the microanatomical organisation of human tissue is lost in isolated cell suspensions. We describe precision-cut human lymph node (LN) slices as architecturally-preserved, functioning lymphoid tissue model system, and explore early inflammatory responses to a potent vaccine liposomal adjuvant containing a TLR4-agonist and QS21 saponin. Combining scRNA-seq, multiplexed immunofluorescence and secretome analysis, we dissect direct and indirect signalling pathways in both leukocytes and stromal cells to reveal communication networks linking innate and adaptive immunity. Application of molecular inhibitors reveals that secretion of IL- 1b, but not IL-18, is TLR4-dependent in human LN. Retaining donor-to-donor immune variation, this ex vivo LN model system enables the study of pathways previously difficult to observe in humans, paving the way towards precision medicine.
diffGEK: Differential Gene Expression Kinetics
Authors: Barile Melania , Chabra Shirom , Isobe Tomoya , Gottgens Berthold
Published: August 2024

A defining characteristic of all metazoan organisms is the existence of different cell states or cell types, driven by changes in gene expression kinetics, principally transcription, splicing and degradation rates. The RNA velocity framework utilizes both spliced and unspliced reads in sin- gle cell mRNA preparations to predict future cellular states and estimate transcriptional kinetics. However, current models assume either constant kinetic rates, rates equal for all genes, or rates completely independent of progression through differentiation. Consequently, current models for rate estimation are either underparametrised or overparametrised. Here we developed a new method (diffGEK) which overcomes this issue, and allows comparison of transcriptional rates across different biological conditions. diffGEK assumes that rates can vary over a trajectory, but are smooth functions of the differentiation process. Analysing Jak2 V617F mutant versus wild type mice for erythropoiesis, and Ezh2 KO versus wild type mice in myelopoiesis, revealed which genes show altered transcription, splicing or degradation rates between different conditions. Moreover, we observed that, for some genes, compensatory changes between different rates can result in comparable overall mRNA levels, thereby masking highly dynamic changes in gene expression kinetics in conventional expression analysis. Collectively, we report a robust pipeline for comparative expression analysis based on altered transcriptional kinetics to discover mechanistic differences missed by conventional approaches, with broad applicability across any biomedical research question where single cell expression data are available for both wild type and treatment/mutant conditions.
Integration of expression datasets to identify biomarkers for accurate Gleason scoring in Prostate Cancer
Authors: Matos-Filipe Pedro , Oliva Baldo , Farrés Judith , Mas José Manuel
Published: August 2024

Prostate cancer is a significant global health issue with considerable mortality rates, emphasising the urgent need for advanced treatment options and improved diagnostic methods. Current diagnostic standards for prostate cancer, including PSA testing and digital rectal examination, often produce false positives, resulting in unnecessary biopsies for patients. This limitation highlights the critical requirement to incorporate more precise biomarkers to enhance diagnostic accuracy and reduce unnecessary procedures. This study aims to investigate biomarker candidates that can effectively determine prostate cancer aggressiveness. By integrating diverse prostate tissue expression datasets and employing machine-learning techniques, this approach seeks to refine diagnostics and provide insights into the molecular underpinnings of the disease, potentially transforming early detection and patient management strategies. Our proposed biomarkers achieve a minimum precision of 0.80, addressing the false positives limitations associated with classical prostate cancer biomarkers. Moreover, the ROC-AUC profiles of most of the candidates proposed in this study align with those exhibited by other innovative biomarkers recently proposed (ROC-AUC ≥ 0.70). We believe these biomarkers are promising candidates for furtherin vivoandin vitroinvestigation.
CARD8 inflammasome activation during HIV-1 cell-to-cell transmission
Authors: Kulsuptrakul Jessie , Emerman Michael , Mitchell Patrick S.
Published: August 2024

Our previous work demonstrated that CARD8 detects HIV-1 infection by sensing the enzymatic activity of the HIV protease, resulting in CARD8-dependent inflammasome activation (Kulsuptrakul et al., 2023). CARD8 harbors a motif in its N-terminus that functions as a HIV protease substrate mimic, permitting innate immune recognition of HIV-1 protease activity, which when cleaved by HIV protease triggers CARD8 inflammasome activation. Here, we sought to understand CARD8 responses in the context of HIV-1 cell-to-cell transmission via a viral synapse. We observed that cell-to-cell transmission of HIV-1 between infected T cells and primary human monocyte-derived macrophages induces CARD8 inflammasome activation in a manner that is dependent on viral protease activity and largely independent of the NLRP3 inflammasome. Additionally, to further evaluate the viral determinants of CARD8 sensing, we tested a panel of HIV protease inhibitor resistant clones to establish how variation in HIV protease affects CARD8 activation. We identified mutant HIV-1 proteases that differentially cleave and activate CARD8 compared to wildtype HIV-1, thus indicating that natural variation in HIV protease affects not only the cleavage of the viral Gag-Pol polyprotein but also likely impacts innate sensing and inflammation.
δ-α cell-to-cell interactions modulate pancreatic islet Ca2+ oscillation modes
Authors: Ren Huixia , Li Yanjun , Xie Beichen , Qian Weiran , Yu Yi , Chang Tianyi , Yang Xiaojing , sneppen kim , Chen Liangyi , Tang Chao
Published: August 2024

Glucose-induced pancreatic islet hormone release is tightly coupled with oscillations in cytoplasmic free Ca2+ concentration of islet cells, which is regulated by a complex interplay between intercellular and intracellular signaling. Delta cells, which entangle with alpha cells located at the islet periphery, are known to be important paracrine regulators. However, the role of delta cells in regulating Ca2+ oscillation pattern remains unclear. Here we show that delta-alpha cell-to-cell interactions are the source of variability in glucose-induced Ca2+ oscillation pattern. Somatostatin secreted from delta cells prolonged the islet's oscillation period in an alpha cell mass-dependent manner. Pharmacological and optogenetic perturbations of delta-alpha interactions led islets to switch between fast and slow Ca2+ oscillations. Continuous adjustment of delta-alpha coupling strength caused the fast oscillating islets to transition to mixed and slow oscillations. We developed a mathematical model, demonstrating that the fast-mixed-slow oscillation transition is a Hopf bifurcation. Our findings provide a comprehensive understanding of how delta cells modulate islet Ca2+ dynamics and reveal the intrinsic heterogeneity of islets due to the structural composition of different cell types.
Spatiotemporal Analysis of Lung Immune Dynamics in LethalCoccidioides posadasiiInfection
Authors: Davalos Oscar A. , Sebastian Aimy , Leon Nicole F. , Rangel Margarita V. , Miranda Nadia , Murugesh Deepa K. , Phillips Ashlee M. , Hoyer Katrina K. , Hum Nicholas R. , Loots Gabriela G. , Weilhammer Dina R.
Published: August 2024

Coccidioidomycosis, or Valley Fever, is a lung disease caused by inhalation ofCoccidioidesfungi, prevalent in the Southwestern U.S., Mexico, and parts of Central and South America. 350,000 cases are reported annually in the U.S., although that number is expected to increase as climate change expands fungal geographic range. While 60% of infections are asymptomatic, the symptomatic 40% are often misdiagnosed due to similarities with bronchitis or pneumonia. A small subset of infection progress to severe illness, necessitating a better understanding of immune responses during lethal infection. Using single-cell RNA sequencing and spatial transcriptomics, we characterized lung responses duringCoccidioidesinfection. We identified monocyte-derivedSpp1-expressing macrophages as potential mediators of tissue remodeling and fibrosis, marked by high expression of profibrotic and proinflammatory transcripts. These macrophages showed elevated TGF-β and IL-6 signaling, pathways involved in fibrosis pathogenesis. Additionally, we observed significant neutrophil infiltration and defective lymphocyte responses, indicating severe adaptive immunity dysregulation in lethal, acute infection. These findings enhance our understanding ofCoccidioidesinfection and suggest new therapeutic targets.

Importance:

Coccidioidomycosis, commonly known as Valley Fever, is a lung disease caused by the inhalation ofCoccidioidesfungi, which is prevalent in the Southwestern U.S., Mexico, and parts of Central and South America. With climate change potentially expanding the geographic range of this fungus, understanding the immune responses during severe infections is crucial. Our study used advanced techniques to analyze lung responses duringCoccidioidesinfection, identifying specific immune cells that may contribute to tissue damage and fibrosis. These findings provide new insights into the disease mechanisms and suggest potential targets for therapeutic intervention, which could improve outcomes for patients suffering from severe Valley Fever.
A toolbox of FRET-based c-di-GMP biosensors and its FRET-To-Sort application for genome-wide mapping of the second messenger regulatory network
Authors: Wang Liyun , Malengo Gabriele , Sanches-Medeiros Ananda , Chen Xuanlin , Teteneva Nataliya , Sierra Silvia González , Hammond Ming C. , Sourjik Victor
Published: August 2024

C-di-GMP is a widespread second messenger, coordinating various cellular functions in bacteria. Levels of c-di-GMP can be highly dynamic and vary over a wide range of concentrations. Here we constructed a large set of FRET-based c-di-GMP biosensors, using homologues of c-di-GMP-binding effector YcgR from different bacterial species. This biosensor library was characterized using a newly established protocol to quantify FRET efficiency using flow cytometry. The resulting toolbox of 18 selected biosensors that undergo large FRET signal change upon c-di-GMP binding displays a ∼100-fold range of c-di-GMP binding affinities. We combined this toolbox with a barcoded Tn5 transposon library and cytometry-based cell sorting to develop FRET-To-Sort, a new application for systematic characterization of gene networks regulating levels of FRET-detected small molecules. Applied to planktonicE. colicells, FRET-To-Sort identified both known and novel regulatory modules controlling c-di-GMP levels, including flagellum and fimbria biogenesis, lipid metabolism and stress response genes.
To integrate or not to integrate: Testing degenerate strategies for solving an accumulation of perceptual evidence decision-making task
Authors: Kopec Charles D , Luo Thomas Zhihao , Bondy Adrian Gopnik , Gupta Diksha , Elliott Verity A , Charlton Julie A , Breda Jessica R , Stagnaro Wynne M , Reyes Emily J , Sirko Adrian I , Bustos Andres F , Willock Jovanna M , Morrison Jessica M , Osorio Klaus L , Brody Carlos D
Published: August 2024

A common approach in the study of cognition is to train subjects to perform a task that requires a particular cognitive process to solve. Analysis of the subjects' response behavior while they perform these tasks can offer valuable insight into the underlying mechanisms that give rise to cognition. However, if subjects are able to accurately perform such a task by using a strategy that doesn't involve the targeted cognitive process, data from those experiments becomes more difficult to interpret. A number of perceptual decision-making tasks have been designed to study the accumulation of evidence, i.e. how noisy information presented over time is used to form a decision. Recent work, however, has highlighted how a variety of non-integration strategies can by some measures yield strikingly near-optimal performance on such tasks, raising the possibility that past conclusions from these experiments may be incorrect. Here we assemble the largest data set of animals performing one such task - the "Poisson Clicks" task - which is optimally solved by the gradual integration of pulsatile auditory noise. To investigate whether rats are in fact using this strategy, we compiled data from 515 rats performing over 35 million trials. We compare performance of 3 degenerate strategies (that circumvent the need to integrate evidence) to the optimal (integration) strategy. We demonstrate that the pulsatile nature of the stimuli used in the Poisson Clicks Task makes it possible to distinguish which strategy subjects use. Overwhelmingly, we find the rats are using an integration strategy when performing the Poisson Clicks Task.
A conserved opal termination codon optimizes a temperature-dependent tradeoff between protein production and processing in alphaviruses
Authors: Bhattacharya Tamanash , Alleman Eva M. , Noyola Alexander C. , Emerman Michael , Malik Harmit S.
Published: August 2024

Alphaviruses are enveloped, single-stranded, positive-sense RNA viruses that often require transmission between arthropod and vertebrate hosts for their sustained propagation. Most alphaviruses encode an opal (UGA) termination codon in nonstructural protein 3 (nsP3) upstream of the viral polymerase, nsP4. The selective constraints underlying the conservation of the opal codon are poorly understood. Using primate and mosquito cells, we explored the role and selective pressure on the nsP3 opal codon through extensive mutational analysis in the prototype alphavirus, Sindbis virus (SINV). We found that the opal codon is highly favored over all other codons in primate cells under native 37ºC growth conditions. However, this preference is diminished in mosquito and primate cells grown at a lower temperature. Thus, the primary determinant driving the selection of the opal stop codon is not host genetics but the passaging temperature. We show that the opal codon is preferred over amber and ochre termination codons because it results in the highest translational readthrough and polymerase production. However, substituting the opal codon with sense codons leads to excessive full-length polyprotein (P1234) production, which disrupts optimal nsP polyprotein processing, delays the switch from minus-strand to positive-strand RNA production, and significantly reduces SINV fitness at 37°C; this fitness defect is relieved at lower temperatures. A naturally occurring suppressor mutation unexpectedly compensates for a delayed transition from minus to genomic RNA production by also delaying the subsequent transition between genomic and sub-genomic RNA production. Our study reveals that the opal stop codon is the best solution for alphavirus replication at 37ºC, producing enough nsP4 protein to maximize replication without disrupting nsP processing and RNA replication transitions needed for optimal fitness. Our study uncovers the intricate strategy dual-host alphaviruses use at a single codon to optimize fitness.
MLL1 directs gut-associated antibody responses to helminth and bacterial infections
Authors: Zhang Yan , Chakma Clarissa , Kirn Alana , Zaini Aidil , Farighi Rohia , Xie Liang , Lopez-Urena Diana , Mileto Steven , Lyras Dena , Zaph Colby , Groom Joanna R. , Good-Jacobson Kim
Published: August 2024

Soil-transmitted helminths are one of the most common infections across the world, yet how to promote an effective humoral response to helminths is not well understood. To ensure the most effective response, molecular programs underpin the specialization of antibody effector subtype to microenvironmental signals. Here, we identify the methyltransferase mixed-lineage leukemia 1 (MLL1) as a key target to promote IgA-driven responses. Mll1 was increased in germinal center (GC) B cells in gut-associated lymphoid tissues, and the absence of MLL1 in mature B cells led to significant reductions in GCs, IgG1 and IgE in response to the helminth Trichuris muris. Yet, worm expulsion occurred more rapidly in Mll1f/fCd23cre/+ mice compared to control mice in the first two weeks of infection. Accelerated worm clearance correlated with significantly elevated IgA+ plasma cells (PC), serum IgA and fecal IgA in in Mll1f/fCd23cre/+ mice. Stimulation of B cells in vitro confirmed that Mll1-deficiency accelerated the formation of IgA+ PC and that this effect was B cell-intrinsic. CCR9 was identified as a key MLL1-regulated molecule by RNA-sequencing and flow cytometry. Correspondingly, Mll1f/fCd23cre/+ mice infected with either T. muris or the bacterium C. rodentium significant increased IgA+CCR9+ PC localized in the large intestine. This tailoring of the B cell response to promote IgA-secreting PC correlated to a healthier microbiome in Mll1f/fCd23cre/+ mice, compared to control mice. Thus, this study reveals MLL1 as a key target to tailor B cell responses to helminth infections, which may aid the development of effective mucosal vaccines or new targeted treatments.
Post-translational modifications on protein VII are important during the early stages of adenovirus infection.
Authors: Arnold Edward A , Smith Julian R , Leung Katie , Nguyen Daniel H , Kelnhofer-Millevolte Laurel E , Guo Monica S. , Smith Jason G. , Avgousti Daphne C
Published: August 2024

Due to the importance of post-translational modification (PTM) in cellular function, viruses have evolved to both take advantage of and be susceptible to such modification. Adenovirus encodes a multifunctional protein called protein VII, which is packaged with the viral genome in the core of virions and disrupts host chromatin during infection. Protein VII has several PTMs whose addition contributes to the subnuclear localization of protein VII. Here, we used mutant viruses that abrogate or mimic these PTMs on protein VII to interrogate their impact on protein VII function during adenovirus infection. We discovered that acetylation of the lysine in positions 2 or 3 (K2 or K3) is deleterious during early infection as mutation to alanine led to greater intake of protein VII to the nucleus and enhanced early gene expression. Furthermore, we determined that protein VII is acetylated at alternative residues late during infection which may compensate for the mutated sites. Lastly, due to the role of the early viral protein E1A in viral gene activation, we investigated the interaction between protein VII and E1A and demonstrated that protein VII interacts with E1A through a chromatin-mediated interaction. Together, these results emphasize that the complexity of virus-host interactions is intimately tied to post-translational modification.
Machine learning model to predict risk assessment of a child inheriting a genetic disorder
Authors: Ramaswamy Medha , Senthilnathan Shreya , Saravanan Adithiyan Rajan Indira , M Snehal , Sivashanmugam Karthikeyan
Published: August 2024

Advancements in Machine Learning (ML) have revolutionised precision medicine, particularly in predicting and preventing genetic disorders. This study provides a comprehensive analysis of ML models designed for the risk assessment of genetic disorders in children, based on clinical history and pedigree analysis. Leveraging a diverse dataset of familial genetic profiles, clinical outcomes, and medical histories, we employed ML algorithms to identify inheritance patterns, assess genetic risks for Mendelian disorders, and predict disease recurrence. The analysis incorporates several ML algorithms, including Gradient Boosting, XGBoost, Random Forest, Logistic Regression, Naive Bayes, and Support Vector Machines (SVM), with the Gradient Boosting model achieving the highest mean cross-validation score of over 0.99. Designed for primary care physicians and healthcare professionals, this model aids in genetic counselling by predicting genetic disorder recurrence based on family history. The paper also addresses ethical and legal considerations, emphasising the importance of genetic counselling and informed decision-making. This tool is intended to support, not replace, medical professionals. This work advances personalised risk assessment for Mendelian single-gene disorders, including autosomal dominant, autosomal recessive, and X-linked recessive disorders, contributing to the field of genomic medicine and facilitating effective family planning strategies.
Gender differences in the attitudes toward cutting people vs pay
Authors: Yoon Yeongjoon , Sengupta Sukanya
Published: August 2024

Purpose

The current research investigates the gender difference in the attitudes of current employees and job seekers (or “future” employees) to payroll cost reduction methods (downsizing vs cutting pay).

Design/methodology/approach

Two studies were conducted. In Study 1, we analyzed a secondary dataset (survey data) of 2,139 employees in Ireland. In Study 2, we conducted an online experiment on 384 people in the US.

Findings

Study 1 reveals that, for males, downsizing survivors' commitment and job satisfaction levels are higher than those of employees whose pay is cut. In contrast, there were no differences in the commitment and job satisfaction levels between survivors of downsizing and pay-reduced employees for females. The analysis in Study 2 indicates that females are more attracted to organizations that utilize pay cuts over downsizing to overcome financial difficulties. In contrast, males demonstrated no differences in job-seeker attraction outcomes to organizations that chose either of these two payroll cost reduction methods. Thus, the results of the two studies indicate that females, compared to males, form less negative (or more favorable) attitudes toward pay cuts over downsizing.

Practical implications

The findings urge organizations to consider gender differences and develop relevant mitigation plans when one method must be chosen to reduce payroll costs.

Originality/value

The outcomes of this research indicate that the selection of a payroll cost reduction method may lead to a disparate impact on gender composition in an organization.
The impact of international internships on Japanese undergraduates’ English achievement: perspectives on cultural capital theory
Authors: Chang Chih-Hao , Utsumi Yuji
Published: August 2024

Purpose

Drawing on the perspectives of cultural capital theory, this study investigated the impact of international internships on the performance of Japanese undergraduates on the Test of English for International Communication (TOEIC) using a between-group pretest-posttest experimental design.

Design/methodology/approach

Students participating in international internships were compared to their counterparts in a noninternational internship control group. Using TOEIC data collected in June 2019 and September 2019, we performed t-tests and estimated a difference-in-differences model with propensity score matching to measure the impacts of participation in international internships, students’ demographic information, family socioeconomic status, and independent learning characteristics.

Findings

The study showed that students’ participation in international internships and independent learning activities had significant effects on TOEIC performance. The findings of this study also indicate that in addition to the effects of international internship experience and independent learning on students’ English performance, learner learning behavior may be important for improving students’ performance.

Research limitations/implications

This empirical research provides meaningful insights for parents, educators, and researchers not only in Japan but also in a broader context in which international internships and independent learning activities have a crucial impact on student performance. It also sheds light on our understanding of the role of activities conceptualized through the lens of cultural capital in educational stratification.

Originality/value

This study elucidates the association among cultural capital theory, international internships, and students’ linguistic achievement and makes an important contribution to the broader conceptual literature.
Promoting education about and for sustainable development: assessing the incorporation of SDGs in Chinese higher education
Authors: Lin Jason Cong
Published: August 2024

Purpose

This study aims to examine and assess how sustainable development goal (SDG) Target 4.7 is incorporated in one leading higher education institution (HEI) in China (with a focus on teacher-education programmes) from students’ perspectives.

Design/methodology/approach

This study uses document analysis and a semi-structured interview to analyse official and accessible documents of the programmes related to SDG Target 4.7 and recorded interviews with seven students across various Postgraduate Diploma in Education programmes in the field of education at the examined university.

Findings

SDG Target 4.7 is absent in the related documents. Challenges and barriers for students include limited opportunity to be informed about SDG Target 4.7, limited topics covered, ineffective pedagogies and students’ diverse needs being neglected and teachers not giving immediate feedback. Given the opportunities in teaching and learning SDG Target 4.7, such as students are keen to learn and implement SDG Target 4.7, future directions could be reducing teachers’ lecturing and increasing student engagement in multiple ways, providing concrete examples that are relevant to students’ lives and giving immediate feedback and designing more related courses to specifically and systematically teach SDG Target 4.7.

Originality/value

This study contributes to the field by identifying and deeply analysing an interesting and representative non-western case that remains underexplored in literature. In this sense, it helps international readers to generate a more comprehensive understanding of Chinese approaches to SDGs in its higher education system, develop a more holistic global discourse on incorporating SDGs into HEIs and compare the similarities and differences between different countries’ approaches.
Government promotion and city image: visitor intentions in Macao
Authors: Zhou Jinquan , Ho Hong-Wai , Mieiro Susana
Published: August 2024

Purpose

This study aims to critically evaluate the impact of government tourism promotion methods on city image and visiting intentions and to explore the moderating effect of tourism experience on two of the conceptualized relationships, using Macao as a case study.

Design/methodology/approach

The research analyzed responses from 407 Macao visitors during the pandemic to determine the effects of tourism promotion methods on the city’s image and visiting intention using structural equation modeling (SEM) to test the hypotheses.

Findings

This study revealed that tourism promotion methods positively impact the city’s image and visiting intentions. City image also mediates the relationship between tourism promotion methods and visiting intentions. Furthermore, tourism experience moderates the relationships between promotion methods and city image and between promotion methods and visiting intentions.

Research limitations/implications

The study’s findings on the effects of promotion methods utilized by local governments support and expand upon existing theoretical frameworks within the realm of nonprofit organizations’ management and marketing for destination marketing organizations (DMOs). However, the cross-sectional design limits causality, and findings may not be generalizable beyond Macao without further comparative research.

Practical implications

This study provides valuable insights for policymakers and marketers to design promotional campaigns that deliver authentic and memorable experiences, aligning with their promotional promises, especially in postpandemic contexts.

Social implications

This research contributes to the theoretical and methodological advancement of management and marketing for DMOs from a public sector perspective, highlighting the critical role of government involvement in urban tourism promotion.

Originality/value

The research offers valuable insights into how promotional activities influence visiting intentions, advancing tourism management and marketing for DMOs from a nonprofit perspective. The study validates theories and adds unique insights by focusing on Macao’s postpandemic recovery, offering practical implications for similar urban settings.
Design and analysis of wheel-tracked composite magnetic adsorption wall-climbing robot
Authors: Xu Minglong , Xue Song , Wang Qionghua , He Shaoxiang , Deng Rui , Li Zenong , Zhang Ying , Li Qiankun , Li Rongchao
Published: August 2024

Purpose

This study aims to improve the stability and obstacle surmounting ability of the traditional wall-climbing robot on the surface of the ship, a wheel-track composite magnetic adsorption wall-climbing robot is proposed in this paper.

Design/methodology/approach

The robot adopts a front and rear obstacle-crossing mechanism to achieve a smooth crossover. The robot is composed of two passive obstacle-crossing mechanisms and a frame, which is composed of two obstacle-crossing magnetic wheels and a set of tracks. The obstacle-crossing is realized by the telescopic expansion of the obstacle-crossing mechanism. Three static failure models are established to determine the minimum adsorption force for the robot to achieve stable motion. The Halbach array is used to construct the track magnetic circuit, and the influence of gap, contact area and magnet thickness on the adsorption force is analyzed by parameter simulation.

Findings

The prototype was designed and manufactured by the authors for static failure and obstacle crossing tests. The prototype test results show that the robot can cross the obstacle of 10 mm height under the condition of 20 kg load.

Originality/value

A new structure of wall-climbing robot is proposed and verified. According to the test results, the wall-climbing robot can stably climb over the obstacle of 10 mm height under the condition of 20 kg load, which provides a new idea for future robot design.
An integrated group decision support framework utilizing Pythagorean fuzzy DEMATEL–CoCoSo approach for medicine cold chain logistics provider selection
Authors: Niu Wenyao , Rong Yuan , Yu Liying
Published: August 2024

Purpose

The purpose of this study is to establish a synthetic group decision framework based on the Pythagorean fuzzy (PF) set to select the optimal medicine cold chain logistics provider (MCCLP). Fierce market competition makes enterprises must constantly improve every link in the process of enterprise sustainable development. The evaluation of MCCLP in pharmaceutical enterprises is an important link to enhance the comprehensive competitiveness. Because of the fuzziness of expert cognition and the complexity of the decision procedure, PF set can effectively handle the uncertainty and ambiguity in the process of multi-criteria group decision decision-making (MCGDM).

Design/methodology/approach

This paper develops an integrated group decision framework through combining the Decision-Making Trial and Evaluation Laboratory (DEMATEL) technique and combined compromise solution (CoCoSo) approach to select a satisfactory MCCLP within PF circumstances. First, the PF set is used to process the ambiguity and uncertainty of the cognition ability of experts. Second, a novel PF knowledge measure is propounded to measure the vagueness of the PF set. Third, a comprehensive criterion weight determination technique is developed through aggregating subjective weights attained utilizing the PF DEMATEL approach and objective weight deduced by knowledge measure method. Furthermore, an integrated MCGDM approach based on synthetic weight and CoCoSo method is constructed.

Findings

The outcomes of sensibility analysis and comparison investigation show that the suggested decision framework can help decision experts to choose a satisfactory MCCLP scientifically and reasonably. Accordingly, the propounded comprehensive decision framework can be recommended to enterprises and organizations to assess the MCCLP for their improvement of core competitiveness.

Originality/value

MCCLP selection is not only momentous for pharmaceutical enterprises to improve transportation quality and ensure medicine safety but also provides a strong guarantee for enterprises to improve their core competitiveness. Nevertheless, enterprises face certain challenges due to the uncertainty of the assessment environment as well as human cognition in the process of choosing a satisfactory MCCLP. PF set possesses a formidable capability to address the uncertainty and imprecision information in the process of MCGDM. Therefore, pharmaceutical enterprises can implement the proposed method to evaluate the suppliers to further improve the comprehensive profit of enterprises.
Ownership structure and financial reporting integrity: the moderating role of earnings quality in Egyptian practice
Authors: Ismail Tariq H. , Samy El-Deeb Mohamed , Abd El–Hafiezz Raghda H.
Published: August 2024

Purpose

This study examines the correlation between ownership structure (OS) and financial reporting integrity (FRI), with emphasis on the impact of earnings quality (EQ) in the Egyptian context.

Design/methodology/approach

The study uses data from 472 firm-year observations of Egyptian publicly listed companies between 2014 and 2021 and carried out descriptive statistics, correlation tests, multiple regression analysis and two-stage least squares (2SLS) to test the hypotheses.

Findings

The results revealed that blockholders and institutional ownership significantly enhance reporting integrity through effective oversight and monitoring. The findings underscore the vital role of concentrated OS in overseeing reporting practices and mitigating managerial opportunism, thereby improving the transparency and reliability of financial disclosures in Egypt.

Practical implications

The findings enrich the literature on corporate governance and financial reporting quality and have important implications for policymakers, regulators and corporate stakeholders.

Originality/value

This work contributes valuable insights on how OS and EQ can bolster FRI, offering crucial information for combating financial crises and facilitating smooth business operations in Egypt.
Distinct actors drive different mechanisms of biopolymer processing in polar marine coastal sediments
Authors: Knittel Katrin , Miksch Sebastian , Moncada Chyrene , Silva‐Solar Sebastian , Moye Jannika , Amann Rudolf , Arnosti Carol
Published: August 2024

Heterotrophic bacteria in the ocean initiate biopolymer degradation using extracellular enzymes that yield low molecular weight hydrolysis products in the environment, or by using a selfish uptake mechanism that retains the hydrolysate for the enzyme‐producing cell. The mechanism used affects the availability of hydrolysis products to other bacteria, and thus also potentially the composition and activity of the community. In marine systems, these two mechanisms of substrate processing have been studied in the water column, but to date, have not been investigated in sediments. In surface sediments from an Arctic fjord of Svalbard, we investigated mechanisms of biopolymer hydrolysis using four polysaccharides and mucin, a glycoprotein. Extracellular hydrolysis of all biopolymers was rapid. Moreover, rapid degradation of mucin suggests that it may be a key substrate for benthic microbes. Although selfish uptake is common in ocean waters, only a small fraction (0.5%–2%) of microbes adhering to sediments used this mechanism. Selfish uptake was carried out primarily by Planctomycetota and Verrucomicrobiota. The overall dominance of extracellular hydrolysis in sediments, however, suggests that the bulk of biopolymer processing is carried out by a benthic community relying on the sharing of enzymatic capabilities and scavenging of public goods.
Pre‐service teachers' preparation for inclusive practices in Cambodia: Experience, self‐efficacy and concerns about inclusion
Authors: Pov Sokunrith , Kawai Norimune
Published: August 2024

This study evaluated the self‐efficacy and concerns regarding inclusive practices among 148 pre‐service teachers enrolled in newly reformed teacher training programmes in Cambodia. It explored variations in pre‐service teachers' concerns and self‐efficacy based on their experience‐related factors. This survey study used the Concern about Inclusive Education Scale (CIES) and Teacher Efficacy for Inclusive Practices (TEIP) scale as research instruments. Data analysis involved descriptive statistics, confirmatory factor analysis, reliability tests and one‐way ANOVA. The findings revealed that while pre‐service teachers had moderate levels of self‐efficacy, they exhibited high levels of concerns about including students with disabilities in regular schools, particularly regarding resources and acceptance. Their concerns and self‐efficacy significantly varied based on their experiences of interacting with individuals with disabilities and teaching students with disabilities. These findings underscore the pressing need for improvements in the new teacher training programmes. Teacher education colleges should align their inclusive education courses with the new inclusive education training guide and make this course compulsory. By emphasising practical skills, incorporating field experience and focusing on local inclusive education policies, pre‐service teachers can be better prepared for inclusive classrooms, thereby enhancing their confidence in implementing inclusive practices.