bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging AlphaFold2 Structural Space Exploration for Generating Drug Target Structures in Structure-Based Virtual Screening
Authors: Uchikawa Keisuke , Furui Kairi , Ohue Masahito
Published: February 2025

In early drug discovery, computational virtual screening (VS) is vital for selecting candidate compounds and reducing costs. However, the lack of experimentally determined 3D structures has limited the application of structure-based VS. Advances in protein structure prediction, notably AlphaFold2, have begun to address this gap. Yet, studies indicate that direct use of AlphaFold2-predicted structures often leads to suboptimal VS performance—likely because these structures fail to capture ligand-induced conformational changes (apo-to-holo transitions). To overcome this, we propose an approach that explores and modifies the structural space of AlphaFold2 predictions to generate conformations more amenable to VS. Our method deliberately alters the multiple sequence alignment (MSA) by introducing alanine mutations at key residues in the ligand-binding site, thereby inducing significant conformational shifts. The exploration process is guided by iterative ligand docking simulations, with mutation strategies optimized either by a genetic algorithm or via random search. Our evaluation shows that when sufficient active compounds are available, the genetic algorithm significantly enhances VS accuracy. In contrast, with limited active compound data, a random search strategy proves more effective. Moreover, our approach is particularly promising for targets that yield poor screening results when using experimentally determined structures from the PDB. Overall, these findings underscore the practical utility of modified AlphaFold2-derived structures in VS and expand the potential of computationally predicted protein models in drug discovery.
SpaFun: Discovering Domain-specific Spatial Expression Patterns and New Disease-Relevant Genes using Functional Principal Component Analysis
Authors: Jiang Xi , Guo Yanghong , Guo Lei , Zhong Lin , Wang Jiayi , Xiao Guanghua , Li Qiwei , Xu Lin
Published: February 2025

SpaFun is a novel, non-model-based method developed to address limitations in existing spatially variable gene (SVG) detection techniques, particularly for large-scale spatially resolved transcriptomics (SRT) datasets. These limitations include computational inefficiency, limited statistical power with increasing data size, and the inability to capture spatial heterogeneity and co-expression patterns among genes. Built on functional principal component analysis (fPCA), SpaFun identifies domain-representative genes (DRGs) with significantly better computational efficiency and greater statistical power while accounting for spatial heterogeneity and co-expression patterns among genes. We applied SpaFun to three SRT datasets and demonstrated that SpaFun outperformed state-of-the-art algorithms for identifying representative genes for tumor regions (e.g., DESeq, edgeR, and limma), as well as recently developed novel algorithms designed for spatial omics to identify the representative genes (e.g., SPARK and CSIDE). This highlights SpaFun’s ability to accurately identify genes most representative of each spatial domain (e.g., tumor, immune, or stroma regions). By uncovering novel disease-relevant genes overlooked by existing algorithms, SpaFun could provide insights into new molecular mechanisms and propose innovative therapeutic strategies to improve patient outcomes.

Key Points

SpaFun is the first method dedicated to identifying DRGs, capturing spatially representative expression patterns within annotated tissue regions, setting it apart from all traditional SVG detection methods.

It leverages fPCA to model gene expression as a function of spatial location, avoiding reliance on predefined spatial distribution assumptions.

The non-model-based framework ensures compatibility with different SRT platforms and experimental designs, making it a scalable and widely applicable tool for SRT research.
Genome modeling and design across all domains of life with Evo 2
Authors: Brixi Garyk , Durrant Matthew G. , Ku Jerome , Poli Michael , Brockman Greg , Chang Daniel , Gonzalez Gabriel A. , King Samuel H. , Li David B. , Merchant Aditi T. , Naghipourfar Mohsen , Nguyen Eric , Ricci-Tam Chiara , Romero David W. , Sun Gwanggyu , Taghibakshi Ali , Vorontsov Anton , Yang Brandon , Deng Myra , Gorton Liv , Nguyen Nam , Wang Nicholas K. , Adams Etowah , Baccus Stephen A. , Dillmann Steven , Ermon Stefano , Guo Daniel , Ilango Rajesh , Janik Ken , Lu Amy X. , Mehta Reshma , Mofrad Mohammad R.K. , Ng Madelena Y. , Pannu Jaspreet , Ré Christopher , Schmok Jonathan C. , John John St. , Sullivan Jeremy , Zhu Kevin , Zynda Greg , Balsam Daniel , Collison Patrick , Costa Anthony B. , Hernandez-Boussard Tina , Ho Eric , Liu Ming-Yu , McGrath Thomas , Powell Kimberly , Burke Dave P. , Goodarzi Hani , Hsu Patrick D. , Hie Brian L.
Published: February 2025

All of life encodes information with DNA. While tools for sequencing, synthesis, and editing of genomic code have transformed biological research, intelligently composing new biological systems would also require a deep understanding of the immense complexity encoded by genomes. We introduce Evo 2, a biological foundation model trained on 9.3 trillion DNA base pairs from a highly curated genomic atlas spanning all domains of life. We train Evo 2 with 7B and 40B parameters to have an unprecedented 1 million token context window with single-nucleotide resolution. Evo 2 learns from DNA sequence alone to accurately predict the functional impacts of genetic variation—from noncoding pathogenic mutations to clinically significantBRCA1variants—without task-specific finetuning. Applying mechanistic interpretability analyses, we reveal that Evo 2 autonomously learns a breadth of biological features, including exon–intron boundaries, transcription factor binding sites, protein structural elements, and prophage genomic regions. Beyond its predictive capabilities, Evo 2 generates mitochondrial, prokaryotic, and eukaryotic sequences at genome scale with greater naturalness and coherence than previous methods. Guiding Evo 2 via inference-time search enables controllable generation of epigenomic structure, for which we demonstrate the first inference-time scaling results in biology. We make Evo 2 fully open, including model parameters, training code, inference code, and the OpenGenome2 dataset, to accelerate the exploration and design of biological complexity.
Detection of mpox clade Ib nucleic-acids in wastewater solids at 147 wastewater treatment plants across the United States
Authors: Boehm Alexandria B. , Wolfe Marlene K. , Bidwell Amanda L. , White Bradley J. , Shelden Bridgette , Duong Dorothea
Published: February 2025

We used a sensitive, specific PCR assay to detect mpox clade Ib DNA in over 3000 wastewater samples collected prospectively across the United States. Mpox clade Ib DNA was detected in one sample from a location with a confirmed case; it was not detected in locations with no confirmed cases.
Enhancing sleep in professional rugby players: observation and sleep interventions
Authors: Goldberg Mathias , Boutin Arnaud , Pairot de Fontenay Benoit , Cohn Joffrey , Michel Valentin , Stauffer Emeric , Debarnot Ursula
Published: February 2025

Sleep is a crucial factor in recovery and must be integrated into athletes’ training plans for optimal performance and well-being. Although professional athletes are advised to sleep for at least 8 hours, many experience shorter sleep durations or poor sleep quality. Sleep interventions have been recently proposed to improve sleep, but their effects remain unclear. This ecological study aimed to evaluate the sleep of a rugby team and to assess the effects of sleep interventions, including sleep hygiene education and relaxation techniques. Thirty-six male professional rugby players were evaluated during two pre- and post-intervention match weeks using objective (actimetric) and subjective (questionnaires) assessments. At baseline, 34 on 36 athletes slept less than 8h per night. Combining both sleep dimensions, 61.1 % of players were considered poor sleepers. After sleep interventions, subjective sleep quality improved (p= 0.001,η2= 0.22), and athletes went to bed earlier (23:28 ± 00:42 vs. 23:43 ± 00:45 during pre-intervention;p= 0.01,η2= 0.15). Positive effects of sleep interventions were especially observed among poor sleepers as their objective sleep quantity increased (405.2 min pre-intervention vs. 425.9 min post-interventionp= 0.004,η2= 0.28). Sleep interventions, composed of theoretical and practical sessions, improved sleep characteristics and might be implemented in athletes’ daily routine. This study offers a simple and accessible method to assess athletes’ sleep, while providing adapted recommendations to optimize or enhance sleep quality and quantity.

Key points

61.1% of the rugby players exhibited both poor sleep quality and quantity during the week and weekends.

Theoretical and practical sleep interventions elicited objective and subjective sleep improvement, especially among poor sleepers.

Sleep assessment and interventions represent an efficient, and feasible method among team-sport players for improving sleep quality.
The Prevalence, Prevention, and Treatment of Cardiovascular Diseases in Twelve African Countries (2014-2019): An Analysis of the World Health Organisation STEPwise Approach to Chronic Disease Risk Factor Surveillance
Authors: Ng’ambi Wingston Felix , Estill Janne , Merzouki Fatma Aziza , Zyambo Cosamas , Beran David , Keiser Olivia
Published: February 2025

Introduction

Cardiovascular diseases (CVDs) are the most common non-communicable diseases (NCDs), responsible for more than 75% of deaths in low- and middle-income countries. We conducted this study to understand the prevalence of history of CVDs, their prevention and treatment in twelve African countries using the WHO NCDs STEPwise survey (STEPS) data.

Methods

We used secondary STEPS data from 12 African countries between 2014 and 2019. A history of heart attack, angina (chest discomfort caused by heart disease), or stroke (cerebrovascular accident or incident) was considered CVD. We fitted logistic regression models to select the predictor variables from a regression model for CVD diagnosis, CVD prevention and CVD treatment binary endpoints.

Results

Amongst 60,294 individuals, the prevalence of CVD was 5%. The CVD prevalence was higher in older individuals, females, individuals with hypertension, smokers, people with high salt intake, and in certain countries. Of the 23,630 individuals at high risk of CVD but without a history of the disease, 11% received prophylactic treatment. Amongst the 2,895 persons with CVDs, 22% received treatment or counselling for CVD: 34% receiving aspirin, 32% counselling for CVD risk factors, 11% statins, and 24% both statins and aspirin. The uptake of CVD treatment varied by hypertension status, sex, age and country.

Conclusion

The prevalence of CVD was relatively low and CVD treatment uptake was sub-optimal. Concerted efforts must be made to accelerate the diagnosis and expand treatment for CVDs in Africa if to curtail untimely deaths attributable to CVDs.
An integrated DNA interactome and transcriptome profiling reveals a PU.1/enhancer RNA-mediated Feed-forward Regulatory Loop Regulating monocyte/macrophage development and innate immune functions
Authors: Waliullah A S M , Qiu Kevin , Dziegielewska Barbara , Tran Minh L. , Nguyen Nicholas N. , Wang Leran , Pan Andrew , Segovia Natalie , Umarino Simone , Zhang Junyan , Nguyen Tuan M. , Craig Jeffrey , Tenen Daniel G. , Trinh Bon Q.
Published: February 2025

High expression of the myeloid master ETS transcription factor PU.1 drives the development of monocyte/macrophage (Mono/MΦ), a crucial cellular component of the innate immune system. Disruptions in normal expression patterns of PU.1 are linked to a variety myeloid malignancy and immune diseases. It is evidenced that PU.1 binds to and modulates enhancers of several myeloid genes. While noncoding RNAs transcribed from noncoding genes at the enhancers are increasingly reported to be involved in enhancer regulation, the crosstalk between PU.1 and noncoding RNAs in enhancer-mediated myeloid gene regulation in Mono/MΦ differentiation and immune response has not been systematically investigated. In this study, we interrogated the PU.1-mediated transcriptome and cistrome with our comprehensive collection of putative and verified enhancers. Among a repertoire of noncoding genes present at PU.1-bound enhancers, we discovered that PU.1 acts as a potent transcription factor inducer of the noncoding RNALOUP, which we previously identified as an RNA inducer of PU.1. The genomic region within theLOUPlocus occupied by PU.1 is characterized by the epigenetic features of a myeloid-specific super-enhancer. Targeted disruption of the PU.1-binding motifs resulted in the downregulation ofLOUPpromoter activity. Depletion ofLOUPreduced the expression of Mono/MΦ cell markers as well as the transcriptional program associated with Mono/MΦ differentiation Mono/MΦ innate defense mechanisms, including phagocytosis, antimicrobial activity, and chemoattractant cytokine production.LOUPinduces Mono/MΦ phagocytic activities. Collectively, our findings indicate that PU.1 and enhancer RNALOUPare biomolecular components of an unidentified feed-forward loop that promotes their mutual expression, contributing to Mono/MΦ differentiation and innate immune functions. The identification of the PU.1/LOUPregulatory circuit provides valuable insights into the mechanisms underlying cell-type and gene-specific enhancer activity and Mono/MΦ biology, as well as significant implications for advancing our understanding of immune diseases and myeloid malignancies.
Optimisation ofRamonda serbicaLEA protein production inEscherichia coliand its secondary structure analysis
Authors: Ana Pantelić , Tatiana Ilina , Dejana Milić , Helena Gradišar , Jelena Radosavljević , Vidović Marija
Published: February 2025

Desiccation, an extreme form of dehydration, reduces the cellular water content to below 5 % and poses a major challenge for most plants.Ramonda serbica, a tertiary relict and homoiochlorophyllous resurrection plant, is an exceptional model for investigating vegetative desiccation tolerance. Late Embryogenesis Abundant (LEA) proteins are strongly involved in this adaptive trait, but their exact molecular function is still unclear. In this study, we report the first successful recombinant production of the desiccation-induced LEA protein, RsLEAP30, from a dicotyledonous resurrection plant species using anEscherichia coliexpression system. By employing immobilised metal affinity and size-exclusion chromatography, we achieved to purify RsLEAP30 to purity over 95 %, providing a robust and scalable method for producing other LEA proteins. Structural characterisation by circular dichroism spectroscopy, combined within silicomodelling, revealed that RsLEAP30 is predominantly disordered but contains α-helical regions. We suggest that this structural duality underpins the protective role of RsLEAP30 in chloroplasts, likely via interactions with thylakoids and desiccation-sensitive proteins within photosynthesis-associated proteins. This function may be crucial for the rapid recovery of photosynthetic components upon rehydration. Our study provides new insights into the structure–function relationship of LEA proteins in resurrection plants and establishes a foundation for future investigations. Understanding the protective mechanisms of RsLEAP30 will pave the way for bioengineering strategies aimed at improving the drought tolerance of crops.
Bdnf-Ntrk2 Signaling Promotes but is not Essential for Spinal Cord Myelination in Larval Zebrafish
Authors: Russell Kristen , Kearns Christina A. , Walker Macie B. , Knoeckel Christopher S. , Ribera Angeles B. , Doll Caleb A. , Appel Bruce
Published: February 2025

Myelin, a specialized membrane produced by oligodendroglial cells in the central nervous system, wraps axons to enhance conduction velocity and maintain axon health. Not all axons are myelinated, and not all myelinated axons are uniformly wrapped along their lengths. Several lines of evidence indicate that neuronal activity can influence myelination, however, the cellular and molecular mechanisms that mediate communication between axons and oligodendrocytes remain poorly understood. Prior research showed that the neurotrophic growth factor Bdnf and its receptor Ntrk2 promote myelination in rodents, raising the possibility that Bdnf and Ntrk2 convey myelin-promoting signals from neurons to oligodendrocytes. We explored this possibility using a combination of gene expression analyses, gene function tests, and myelin sheath formation assays in zebrafish larvae. Altogether, our data indicate that, although not essential for myelination, Bdnf-Ntrk2 signaling contributes to the timely formation of myelin in the developing zebrafish spinal cord.
Oculocutaneous albinism variants in 28 consanguineous families and functional classification of a pathogenic deep intron variant inTYR
Authors: Farooq Muhammad , Bruun Gitte Hoffmann , Sarusie Menachem V. K. , Kessel Line , Akhtar Hamna , Abdullah Uzma , Anjum Iram , Doktor Thomas K. , Andresen Brage Storstein , Baig Shahid Mahmood , Larsen Lars Allan , Grønskov Karen
Published: February 2025

Oculocutaneous albinism (OCA) is genetically and clinically heterogeneous recessive disorders with at least 23 associated genes. Isolated OCA is characterized by hypopigmentation in the skin, hair, and eyes combined with ocular abnormalities. Hermansky Pudlak syndrome (HPS) and Chediak-Higaski syndrome are syndromic forms of OCA, distinguished by immunological and hematological symptoms in addition to hypopigmentation and ocular anomalies. Targeted clinical care is crucial for the patients and molecular genetic diagnosis is important for classification of patients. Current diagnostic yield is approximately 70%, and a high prevalence of patients, heterozygous for pathogenic variants in OCA genes, might suggest presence of disease-causing non-coding variants.

We describe here NGS analysis, including CNV analysis, of 28 consanguineous families, comprising a total of 136 individuals presenting with OCA. We provide a molecular genetic diagnosis in all 28 families. Noteworthy, five families (18 %) had pathogenic variants in a gene associated with HPS. Furthermore, we report the first deep intron variant inTYRcausing OCA and show by minigene analysis that the variant causes inclusion of a pseudoexon.
Epigenetic Regulation During Flatfish Metamorphosis: Integrative Omics Analysis of DNA Methylation and Gene Expression in Turbot Brain
Authors: Guerrero-Peña Laura , Suarez-Bregua Paula , Sánchez-Baizán Núria , Piferrer Francesc , Tena Juan J. , Rotllant Josep
Published: February 2025

The regulation of gene expression plays a pivotal role in the complex metamorphic process of flatfishes, which oversees the dynamic alterations that occur during their transition from a pelagic to a benthic way of life. Flatfish metamorphosis is characterized by substantial modifications in both form and function, which are initiated by thyroid hormones. Epigenetic mechanisms play a vital role in the regulation of gene expression during this transformative process. This study examines the molecular mechanisms underlying flatfish metamorphosis by integrating multi-omics data that provide information on chromatin status, DNA methylation profile, and gene expression at three key stages (pre-metamorphosis, climax and post-metamorphosis) in the turbot (Scophthalmus maximus) brain, a complex organ that plays a critical role in the regulation of this intricate process. The analysis of DNA methylation patterns revealed major epigenetic dynamic changes during the different metamorphosis stages. Specifically, the methylation levels exhibited a typical bimodal distribution in the pre-metamorphic stage, transitioned to intermediate levels of methylation (around 50%) during the climax stage, and reverted to a bimodal distribution in the post-metamorphic stage. Notably, DMRs were identified in regions of open chromatin that colocalized with CpG islands. Moreover, our results indicate an inverse relationship between DNA methylation and transcriptional activity in regions near the transcription start sites (TSSs), where high levels of methylation correspond to low expression and low levels of methylation corresponds to high gene transcription. This study thereby elucidates the regulatory impact of methylation on gene expression during the metamorphosis process in the flatfish brain.
Bioactive Flavonoid Extract Suppresses NLRP3 Activation and Inflammation in 2D and 3D Lung Models
Authors: El Sabbagh Dana El Soufi , de Souza Diulie Valente , Pappis Lauren , Davidson Carolina Bordin , Mangos Maria , Wang Aizhou , Cypel Marcelo , Attisano Liliana , Machado Alencar Kolinski , Andreazza Ana Cristina
Published: February 2025

Inflammasome activation plays a critical role in lung inflammation, with the NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) inflammasome serving as a key mediator of inflammatory cytokine release and pyroptotic cell death. This study investigates the effects of a bioactive flavonoid extract (BFE), as a potential modulator of NLRP3-mediated inflammation using THP-1 derived macrophages, A549 lung cells (2D cells), and lung organoids (3D cells). Cells were primed with lipopolysaccharide (LPS), treated with BFE, and then activated with nigericin to induce NLRP3 activation and examine BFE’s effects. Markers of inflammation, including presence of ASC specks (3D models), reactive oxygen species production (ROS) (2D models), caspase-1 activity (2D and 3D models), and IL-1β release (2D and 3D models) were measured to assess the extent of inflammasome activation in several treatment conditions. By integrating 2D and 3D lung models, this work provides insight into the NLRP3 inflammasome axis in lung inflammation and explores BFE as a potential therapeutic strategy for inflammasome-driven pulmonary inflammatory processes.
First Use of Phage Therapy in Canada for the Treatment of a Life-Threatening, Multidrug-ResistantStaphylococcus epidermidisPeriprosthetic Joint Infection: An N-of-1 Trial
Authors: Cammuso Melissa T. , Cook Bradley W. M. , Cameron D. William , Ryan Stephen , Suh Gina A. , Azad Marisa A.
Published: February 2025

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistantStaphylococcus epidermidiship PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDRS. epidermidis. We developed a novel phage protocol for this patient, with twice daily, intra-articular and intravenous (7 x 109PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Ten months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.
Investigating E3 ubiquitin ligase activity of ORF150 in fish herpesvirus pathogenesis
Authors: Wang Hao , Yang Jia , Li Mengjuan , Zhang Ye , Lu Liqun
Published: February 2025

Fish herpesviruses, members of the familyAlloherpesviridae, infect aquatic species. The host’s ubiquitin-proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays a crucial role in the viral replication cycle. Viruses exploit the UPS to facilitate their replication and evade host immune responses. This study demonstrated that cyprinid herpesvirus 2 (CyHV-2) infection significantly activates the host UPS pathway, as revealed by transcriptomics sequencing analysis. Further, treatment with MG132, a proteasome inhibitor, markedly downregulates intracellular viral replication and gene transcription. Additionally, we identified a novel, highly conserved E3 ubiquitin ligase with a C3HC4-type really interesting gene (RING)-finger (RING-HC) domain, encoded by open reading frame 150 (ORF150) of CyHV-2. These findings provide critical molecular evidence that the host UPS is essential for fish herpesvirus replication and suggest that viral E3 ligases may serve as potential targets for new antiviral strategies.
Human monoclonal antibodies that target clade 2.3.4.4b H5N1 hemagglutinin
Authors: Alzua Garazi Peña , León André Nicolás , Yellin Temima , Bhavsar Disha , Loganathan Madhumathi , Bushfield Kaitlyn , Brouwer Philip J.M. , Rodriguez Alesandra J. , Jeevan Trushar , Webby Richard , Marizzi Christine , Han Julianna , Ward Andrew B. , Duty J. Andrew , Krammer Florian
Published: February 2025

The highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds and mammals, including infection in humans, raising concerns about its pandemic potential. We aimed to generate a panel of anti-hemagglutinin (HA) human monoclonal antibodies (mAbs) against the H5 protein of clade 2.3.4.4b. H2L2 Harbour Mice®, which express human immunoglobulin germline genes, were immunized with H5 and N1 recombinant proteins from A/mallard/New York/22-008760-007-original/2022 H5N1 virus, enabling the generation of human chimeric antibodies. Through hybridoma technology, sixteen full human mAbs were generated, most of which showed cross-reactivity against H5 proteins from different virus variants. The functionality of the sixteen mAbs was assessedin vitrousing hemagglutination inhibition and microneutralization assays with viruses containing a clade 2.3.4.4b HA. Fourteen out of the sixteen mAbs neutralized the virusin vitro. The mAbs with the strongest hemagglutination inhibition activity also demonstrated greater neutralizing capacity and showed increased protective effectsin vivowhen administered prophylactically or therapeutically in a murine H5N1 challenge model. Using cryo-electron microscopy, we identified a cross-clonotype conserved motif that bound a hydrophobic groove on the head domain of H5 HA. Akin to mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus 2019 (COVID-19) pandemic, these mAbs could serve as important treatments in case of a widespread H5N1 epidemic or pandemic.
RB-TnSeq elucidates dicarboxylic acid specific catabolism in β-proteobacteria for improved plastic monomer upcycling
Authors: Pearson Allison N. , Lynch Julie M. , Ho Cindy N. , Hudson Graham A. , Roberts Jacob B. , Menasalvas Javier , Vilchez Aaron A. , Incha Matthew R. , Schmidt Matthias , Mukhopadhyay Aindrila , Deutschbauer Adam M. , Thompson Mitchell G. , Shih Patrick M. , Keasling Jay D.
Published: February 2025

Dicarboxylic acids are key components of many polymers and plastics, making them a target for both engineered microbial degradation and sustainable bioproduction. In this study, we generated a comprehensive dataset of functional evidence for the genetic basis of dicarboxylic and fatty acid metabolism using randomly-barcoded transposon sequencing (RB-TnSeq). We identified four β-proteobacteria that displayed robust growth with dicarboxylic acid sole carbon sources and cultured their mutant libraries with dicarboxylic and fatty acids with carbon chain lengths from C3 to C12. The resulting fitness data suggested that dicarboxylic and fatty acid metabolisms are largely distinct, and different sets of β-oxidation genes are required for catabolizing dicarboxylic versus fatty acids of the same carbon chain lengths. Additionally, we identified transcriptional regulators and transporters with strong fitness phenotypes related to dicarboxylic acid utilization. InRalstonia sp.UNC404CL21Col (R. CL21), we deleted two transcriptional repressors to improve its utilization of short chain dicarboxylic acids. We exploited the diacid-utilizing catabolism ofR. CL21to upcycle a mock mixture of the dicarboxylic acids produced when polyethylene is oxidized. After introducing a heterologous indigoidine production pathway, this engineeredRastoniaproduced 0.56 ± 0.02 g/L indigoidine from a mixture of dicarboxylic acids as a carbon source, demonstrating the potential ofR. CL21to upcycle plastics waste to products derived from tricarboxylic acid (TCA) cycle intermediates.

Importance

Upcycling the carbon in plastic wastes to value-added products is a promising approach to address the plastics waste and climate crises, and dicarboxylic acid metabolism is an important facet of several approaches. Improving our understanding of the genetic basis of this metabolism has the potential to uncover new enzymes and genetic parts for engineered pathways involving dicarboxylic acids. Our dataset is the most comprehensive interrogation of dicarboxylic acid catabolism to date, and this work will be of utility to researchers interested in both plastics bioproduction and upcycling applications.
Evaluation of Metagenome Binning: Advances and Challenges
Authors: Arangasamy Yazhini , Morice Étienne , Jochheim Annika , Lieser Benjamin , Söding Johannes
Published: February 2025

Background

Several recent deep learning methods for metagenome binning claim improvements in the recovery of high quality metagenome-assembled genomes. These methods differ in their approaches to learn the contig embeddings and to cluster them. Rapid advances in binning require rigorous benchmarking to evaluate the effectiveness of new methods. We have benchmarked newly developed state-of-the-art deep learning binners on CAMI2 datasets, including our own, McDevol.

Results

The results show that COMEBin and GenomeFace give the best binning accuracy, although not always the best embedding accuracy. Interestingly, post-binning reassembly consistently improves the quality of low coverage bins. We find that binning coassembled contigs with multi-sample coverage is effective for low coverage dataset while binning multi-sample contigs with multi-sample coverage (‘multi-sample’) is effective for high-coverage samples. In multi-sample binning, splitting the embedding space by sample before clustering showed enhanced performance compared to the standard approach of splitting final clusters by sample.

Conclusions

COMEBin and GenomeFace emerged as the top-performing tools overall, with MetaBAT2 and GenomeFace demonstrating superior speed. To facilitate future development, we provide workflows for standardized benchmarking of metagenome binners.
Stochastic Regression and Peak Delineation with Flow Cytometry Data
Authors: Kearsley Anthony J. , Parratt Kirsten H. , Pinheiro Guilherme L. , Da Silva Sandra M.
Published: February 2025

Many modern molecular analysis methods utilize DNA content values as part of the measurement process, and thus, the distribution of genome copies per cell within a population of cells is important. Genome copy distributions can be measured via flow cytometry by thresholding (or “gating”) a subset of cells from which estimates of the targeted properties (e.g., genome copy number) can be calculated. This manuscript introduces a new approach that gives separate estimates of signal and noise, the former of which is used for gating and analysis, and the latter is used to quantify uncertainty. In this approach stochastic regression was used to quantify subpopulations of cells that have distinctly different genome copies per cell within a heterogenous population ofEscherichia coli(E. coli)cells. By separating the signal and noise components, they can be used independently to evaluate measurement quality across different experimental conditions.
A scalable approach to investigating sequence-to-expression prediction from personal genomes
Authors: Spiro Anna E. , Tu Xinming , Sheng Yilun , Sasse Alexander , Hosseini Rezwan , Chikina Maria , Mostafavi Sara
Published: February 2025

A key promise of sequence-to-function (S2F) models is their ability to evaluate arbitrary sequence inputs, providing a robust framework for understanding genotype-phenotype relationships. However, despite strong performance across genomic loci, S2F models struggle with inter-individual variation. Training a model to make genotype-dependent predictions at a single locus—an approach we call personal genome training—offers a potential solution. We introduce SAGE-net, a scalable framework and software package for training and evaluating S2F models using personal genomes. Leveraging its scalability, we conduct extensive experiments on model and training hyperparameters, demonstrating that training on personal genomes improves predictions for held-out individuals. However, the model achieves this by identifying predictive variants rather than learning acis-regulatory grammar that generalizes across loci. This failure to generalize persists across a range of hyperparameter settings. These findings highlight the need for further exploration to unlock the full potential of S2F models in decoding the regulatory grammar of personal genomes. Scalable software and infrastructure development will be critical to this progress.
The impact of self-service technologies on customer engagement in Nigerian fuel stations: exploring the roles of corruption mitigation and trust
Authors: Anka Rashida Bello , Shamim Amjad
Published: February 2025

Purpose

This study aims to investigate the impact of customer willingness to adopt self-service technologies (SST) in the Nigerian fuel station context. Specifically, it explores the interplay between corruption mitigation at fuel stations, customer trust and customer intimacy in shaping the attitudes towards SST adoption.

Design/methodology/approach

The research employs a quantitative approach; partial least squares structural equation modelling (PLS-SEM) software was conducted using an online survey sample of 233 participants from Nigeria.

Findings

The research reveals that customer willingness to use SST positively correlates with customer trust, corruption mitigation and customer intimacy when introduced at fuel stations. However, as anticipated by the study, corruption mitigation at fuel stations and customer trust significantly mediate the relationship between willingness to use SST and customer intimacy. This suggests that an increase in customers’ willingness to use SST at a fuel station not only enhances the chances of mitigating corruption but also strengthens customer trust.

Originality/value

This study contributes to both academic understanding and practical implications. It advances the literature on technology adoption by exploring the unique context of Nigerian fuel stations. The study’s originality lies in its examination of these dynamics within a specific cultural and operational setting, presenting valuable knowledge for both researchers and fuel station managers seeking to improve customer experiences and service quality.
Organizational climate for initiative and innovative work behavior: a moderated mediation model
Authors: Hassi Abderrahman , Rohlfer Sylvia , Jebsen Simon
Published: February 2025

Purpose

This paper aimed at investigating the relationship between organizational climate for initiative, job autonomy, climate for innovation and innovative work behavior (IWB) in a developing economy context.

Design/methodology/approach

The study surveyed 444 manufacturing businesses in Morocco, collecting data from three sources: CEOs, middle managers and non-managerial employees in the production department. The data were analyzed using structural equation modelling, the Bayesian estimation approach and the bootstrapped moderated mediation technique.

Findings

This study revealed that middle managers’ job autonomy mediates the positive link between climate for initiative and middle managers’ IWB when climate for innovation is strong.

Practical implications

This study provides practical information for organizations intending to make their middle managers willing to be innovative in their job by granting them job autonomy and building favorable climates for initiative and innovation.

Originality/value

This research expands the human resource management and innovation literature by examining features of the work context (i.e. climates for initiative and for innovation, and job autonomy) as previous research has mainly focused on the context approach to work design (i.e. social environment of work design). The study highlights the role of middle managers as essential contributors to fostering innovations within their firms.
What drives Millennials and Generation Z to adopt cryptocurrency for hotel payments?
Authors: Moon Jehun , Erdem Mehmet , Ozdemir Ozgur , Kim Hyelin (Lina) , Anlamlier Eda
Published: February 2025

Purpose

This study aims to investigate and compare the factors that affect Millennials and Generation Z (Gen Z) hotel guests’ intention to adopt cryptocurrency payments (CPs) when booking a hotel.

Design/methodology/approach

A sequential mixed-methods approach was used. Study 1 included 20 semi-structured interviews. The qualitative findings subsequently informed the design of a quantitative survey in Study 2, conducted with 604 participants. Additionally, the authors examined the moderating effect of generational differences.

Findings

Through a thematic analysis, Study 1 identified six predetermined factors from the innovation diffusion theory and the unified theory of acceptance and use of technology – trialability, observability, performance expectancy, effort expectancy, facilitating conditions and social influence – and two additional elements – personal innovativeness and perceived risk. Study 2 quantitatively examined that all eight factors were significant predictors of intention to adopt CPs among Millennials and Gen Z hotel guests. Furthermore, the findings from the comparative analysis based on the generational cohort theory indicated that generational differences moderated the relationships among performance expectancy, effort expectancy and personal innovativeness and adoption intention.

Practical implications

The results of this study offer actionable insights for hotel operators and policymakers aiming to expedite CP adoption among Millennials and Gen Z hotel guests.

Originality/value

To the best of the authors’ knowledge, this study is among the first studies to comprehensively identify the determinants and their significance differences in Millennials and Gen Z hotel guests’ intentions to adopt CPs via a sequential mixed-methods approach.
Exploring cultural influences on national alcoholic beverage purchases: a full latent variable structural equation model
Authors: Adžić Slobodan
Published: February 2025

Purpose

This study aims to achieve two key objectives. The initial objective is to construct a full latent structural equation model (SEM) for examining the cultural influences on the consumer purchasing habits of rakija, a culturally endorsed alcoholic beverage in Serbia. The second objective is to assess qualitatively the model’s suitability for analyzing alcoholic beverages that are culturally specific and nationally recognized rather than universally applicable.

Design/methodology/approach

Data for this study are collected online via a survey method. The sample consists of 393 (n = 393) rakija consumers.

Findings

The main finding of this study is that culture significantly influences consumer behavior and purchasing habits regarding a national drink, not only directly but also through its mediators. Moreover, the results of the multigroup analysis confirmed that the group of rakija drinkers who preferred this culturally and nationally endorsed beverage differed significantly from the group of rakija drinkers who still preferred beer.

Originality/value

The final SEM demonstrates broader applicability and can be used to examine the purchasing tendencies of alcoholic beverages in various nations, as long as they possess cultural significance and heritage.
The influence of digitalization on international marketing decision: evidence from Chinese private enterprises
Authors: Liu Dewen , Zou Ying , Lv Peng , Yao Shanji
Published: February 2025

Purpose

While the impact of digitalization on businesses has been extensively studied, the influence of digitalization on marketing outcomes in private enterprises has not received sufficient attention. The current study aims to examine how and when digitalization affects international marketing decisions in the context of private enterprises.

Design/methodology/approach

This study employs data from a survey of Chinese private enterprises conducted in 2020, which constitutes the world's largest dataset of its kind. Nearly 19,000 samples were included in the study. Additionally, we also incorporate supplementary data on digitalization in the Chinese region. Employing various methods, this study empirically and robustly examines the proposed research framework within the context of Chinese private enterprises.

Findings

Based on the resource-based view and agency theory, this paper found that digitalization can positively impact private enterprises’ direct and indirect international marketing decisions. Furthermore, we introduce the inclusion of innovation capacity and board governance as moderators in the model and find that board governance attenuates the influence of digitalization on international marketing decisions, while innovation capacity enhances the impact of digitalization on direct international marketing but diminishes its effect on indirect international marketing.

Originality/value

This study advances the understanding of the impact of digitalization on international marketing in private enterprises, thereby addressing the gap in the limited focus on digitalization in private enterprises. It also demonstrates how private enterprises effectively utilize digitalization to gain marketing advantages in the international market.
Tri Hita Karana: Balinese local wisdom and its role in the triumph over corruption
Authors: Ardiana Putu Agus , Sujana I Ketut , Natalia Sang Ayu Putu Dinda , Yanthi Kadek Dwi Linda
Published: February 2025

Purpose

This study aims to examine how integrating Tri Hita Karana principles – Parahyangan (spiritual harmony), Pawongan (social harmony) and Palemahan (environmental harmony) – influences accounting practices and organisational change to combat corruption in Bali’s government institutions, with potential broader applications.

Design/methodology/approach

Semi-structured interviews with 21 departmental leaders were analysed using thematic analysis to understand how Tri Hita Karana principles are embedded in accounting and governance practices.

Findings

The integration of Tri Hita Karana principles fosters ethical behaviour, transparency and accountability. Parahyangan strengthens spiritual accountability in financial reporting, Pawongan enhances collaborative oversight and Palemahan promotes sustainable decision-making, reducing corruption linked to resource misuse. These principles offer a holistic anti-corruption approach that extends beyond compliance, showing potential adaptability in diverse contexts.

Research limitations/implications

While context-specific to Bali, the Tri Hita Karana principles reflect universal values of integrity and sustainability. Further research is needed to adapt these principles to different cultural and organisational environments.

Practical implications

Insights from this study guide policymakers in incorporating cultural values into governance to enhance ethical practices, especially in regions with weak regulatory frameworks.

Social implications

This study highlights how local wisdom like Tri Hita Karana can drive ethical governance, providing a model adaptable to various contexts for sustainable anti-corruption efforts.

Originality/value

This study shows how cultural values can enhance anti-corruption efforts, offering a framework adaptable to diverse global settings.
A comparative bibliometric analysis of research articles on garment production
Authors: Sun Qi , Zhang Ying , Sun Yue , Chen Yi-Jun , Li Xin , Huang Qian-Wen , Li Qi-Zheng , Wang Laili
Published: February 2025

Purpose

With the accumulation of theoretical research and practical experience in the field of garment production research, it is imperative to methodically analyze and reflect on the achievements that have been made. This review aims to systematically map the academic landscape of research articles on garment production, elucidate the evolutionary trajectory of this discipline, identify emerging research frontiers and provide insights into its prospects.

Design/methodology/approach

Based on the Web of Science core database, 307 research articles were systematically analyzed by CiteSpace software. The study employed bibliometric and thematic analyses to offer in-depth insights into the dynamics and evolution of research on garment production.

Findings

Results reveal that keyword analysis emphasizes the significance of topics such as apparel assembly line, lean production, circular economy, fuzzy logic, global production networks, social sustainability and supply chain management in garment production research. Citation analysis demonstrates that articles related to environmental impact, supply chain management, production process and production technology constitute the knowledge base and core of garment production research. Eight principal research themes emerge: customized garment production, production technology, quality assurance, equipment, production lines, supply chain management, environmental impact and social and human impact. Future research hotspots will focus more on sustainable, intelligent and digital clothing production.

Originality/value

The findings systematically sort out the hotspots and trends in garment production, establish knowledge structures and display them through intuitive representations. The rich insights set the stage for the development of garment production and provide future guidance for theoretical research.
It was only supposed to be temporary: exploring assigned expatriates’ decision to becoming long-term migrants in their host country
Authors: Hong Sungah , Richardson Christopher , Abdul Rahim Noor Fareen
Published: February 2025

Purpose

The purpose of this paper is to examine push and pull factors influencing assigned expatriates’ (AEs) decision to remain in their host countries indefinitely as long-term migrants.

Design/methodology/approach

In-depth semi-structured interviews were conducted with 14 individuals from different developed countries on renewable visas in their host country of Malaysia, having arrived initially as AEs. Interview data were analyzed using a thematic analysis approach.

Findings

The findings highlight push and pull factors and suggest that AEs’ decisions to become long-term migrants can be attributed to three contextual factors: personal, organizational and country.

Practical implications

This study provides insights for human resource managers to understand potential motivating factors that might influence an AE to consider remaining indefinitely in their host country as a long-term migrant, thus terminating their contract with their MNC employer.

Originality/value

This is among the first empirical studies in the field of international business on AEs who subsequently became long-term migrants in a host country. Moreover, it highlights the possible change in expatriates’ temporary status. It contributes to global mobility literature by examining how in highly skilled professionals, the pursuit of a long-term professional career and lifestyle improvement correlates with a “privileged” position in a host country.