bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrasting genomic responses of hydrothermal vent animals and their symbionts to population decline after the Hunga volcanic eruption
Authors: Breusing Corinna , Hauer Michelle A , Hughes Ian V , Becker Johann S , Casagrande David , Phillips Brennan T , Girguis Peter R , Beinart Roxanne A
Published: February 2025

Genetic bottlenecks are evolutionary events that reduce the effective size and diversity of natural populations, often limiting a population's ability to adapt to environmental change. Given the accelerating human impact on ecosystems worldwide, understanding how populations evolve after a genetic bottleneck is becoming increasingly important for species conservation. Ash deposits from the 2022 Hunga volcanic eruption in the Southwest Pacific led to a drastic decline of animal symbioses associated with hydrothermal vents in this region, allowing insights into the effects of population bottlenecks in the deep sea. Here, we applied metagenomic sequencing to pre- and post-eruption samples of mollusk-microbial symbioses from the Lau Basin to investigate patterns of genetic variation and effective population size. Our data indicate that animal host populations currently show only small changes in genome-wide diversity but in most cases experienced a long-term decline in effective size that was likely intensified by the volcanic impact. By contrast, symbiont populations exhibited a notable decrease in genomic variation, including loss of certain habitat-specific strains. However, detection of environmental symbiont sequences suggests that lost strain diversity might be recovered from the free-living symbiont pool. The differences between host and symbiont populations might be related to their contrasting genetic structures and levels of gene flow, although the full extent of population bottlenecks in the host animals might only be recognizable after a few generations. These results add to our understanding of the evolutionary dynamics of animal-microbe populations following a natural disturbance and help assess their resilience to potential future anthropogenic impacts.
Accelerated genome shuffling associated with rapid evolution of sexual conflict in seed beetles
Authors: Chen Weiyao , Zhao Jinshuai , Lin Miaojin , Liu Changyou , Xie Liqiang , Wang Lixia , Zhang Xiaoming , Liao Yi , Chen Jinfeng
Published: February 2025

Structural variation (SV) has an extensive impact on the evolution of the genome. The diverse SV provide a material basis for genome evolution, which can affect gene expression, 3D genome structure, and even changes in complex chromosomal features through regional recombination, copy number variation, and chromosome rearrangement. Here, we assemble and compare the chromosome-level assemblies of three species (Acanthoscelides obtectus, Callosobruchus chinensis, and C. maculatus) in Bruchinae, a clade of Coleoptera that is often used as models to study sexual conflict, to investigate the influence of SV on the changes of various genomic characteristics during species evolution. Through comparative genomic analysis of Coleoptera species, we reveal extensive structural variants (SVs) within the Bruchinae family, which is linked to the ongoing activity of LINE transposons. We show that SV drive the rapid evolution of sex chromosomes and correlated with dynamic evolution of sex-biased gene expression in seed beetle species. Our analysis highlights the acquisition of novel genes on the Y chromosome through frequent gene translocations, gradually shaping them into genes exhibiting male-biased expression patterns. This underscores the Y chromosome's role in promoting sexual dimorphism evolution. Our findings reveal the significant contributions of SV to genome evolution, specifically through their influence on sex chromosome evolution and the evolutionary dynamics of sex-biased genes.
PepGo: a deep learning and tree search-based model for de novo peptide sequencing
Authors: Chang Yuqi , Kristiansen Karsten , Liu Siqi
Published: February 2025

Identifying peptide sequences from tandem mass spectra is a fundamental problem in proteomics. Unlike search-based methods that rely on matching spectra to databases, de novo peptide sequencing determines peptides directly from mass spectra without any prior information. However, the design of models and algorithms for de novo peptide sequencing remains a challenge. Many de novo approaches leverage deep learning but primarily focus on the architecture of neural networks, paying less attention to search algorithms. We introduce PepGo, a de novo peptide sequencing model that integrates Transformer neural networks with Monte Carlo Tree Search (MCTS). PepGo predicts peptide sequences directly from mass spectra without databases, even without prior training. We show that PepGo surpasses existing methods, achieving state-of-the-art performance. To our knowledge, this is the first approach to combine deep learning with MCTS for de novo peptide sequencing, offering a powerful and adaptable solution for peptide identification in proteomics research.
A large-scale genome-wide association meta-analysis for nevus count provides direct insights into the genetics of melanoma
Authors: Jayasinghe G J M S R , Zhu Gu , Pandeya Nirmala , Olsen Catherine M , Martin Nicholas G , Lind Penelope A , Medland Sarah E , Gordon Scott D , Torres Santiago D , Lingham Gareth , Lee Samantha S Y , Nijsten Tamar , Kayser Manfred , Pardo Luba M. , Montgomery Grant W , Hayward Nicholas K , Palmer Jane M , Hunter David J , Han Jiali , Hewitt Alex W , Falchi Mario , Bishop D Timothy , Brown Kevin M , Bataille Veronique , Mackey David A , Iles Mark M , Whiteman David C , Duffy David L , MacGregor Stuart , Law Matthew H
Published: February 2025

A greater understanding of the biology of nevi will provide insights into the etiology of melanoma. Our large-scale meta-analysis of 14 nevus genome-wide association study (GWAS) included 85,967 individuals of European ancestry. We identified 29 nevus-associated loci (p < 5×10−8), of which 24 were not previously reported in a GWAS conducted for nevus count alone. We further identified 255 candidate genes for nevus loci, includingSIKE1which is involved in immune response regulation. This is of interest because immune response regulation influences the formation of nevi and melanoma susceptibility. Gene-set enrichment analyses prioritised immune response-related pathways and cancers that do not have a pigmentation component (e.g. breast, prostate, and glioma). This suggests that the biology underlying nevus count captures risk pathways beyond pigmentation that are relevant to melanoma. A nevus polygenic risk score explains 5% of the variance in nevus count, indicating its potential to enhance melanoma risk prediction.
Indonesian Version Of The Perceived Stress Scale- 10 (IPSS): A Psychometric Properties Of The Indonesian PSS-10 in Adolescents With Obesity
Authors: erlena Erlena Erlena , Nurjannah Intansari Nurjannah , Achadiono Deddy Nurwachid , Wibawa Tri , Prihastari Lisa
Published: February 2025

Introduction: Stress significantly impacts adolescent obesity, which may impact both physical and mental health outcomes. One popular tool for measuring perceived stress is the Perceived Stress Scale-10 (PSS-10). The purpose of this study is to evaluate the validity and reliability of the Indonesian version of the PSS-10 (IPSS) in this demographic.Methods: Participants of 297 adolescents with and without obesity diagnoses. The scale was translated into Indonesian using the translation-back translation technique. For convergent validity, participants filled out the Indonesian PSS-10 and associated psychological tests. The factor structure of the scale was assessed using confirmatory factor analysis (CFA). Cronbach's alpha was used to determine internal consistency, and a group of individuals was evaluated for test-retest reliability over two weeks. Results: The Indonesian conflict of interest nothing declared PSS-10 demonstrated good internal consistency (Cronbach's alpha = 0.862) and CFA supported the two-factor model had acceptable fit indices ( CFI-0.950, RMR- 0.085, RMSE= 0.072) consistent with the original scale, indicating satisfactory construct validity  Convergent validity was confirmed through significant correlations with related psychological constructs. Discussion: According to the results, the PSS-10 in Indonesia is a viable and dependable instrument for assessing felt stress in obese teenagers. The tool can be used to understand better the factors associated with stress in this group in both clinical and research settings. Future studies should examine the predictive validity of the scale and how well it applies to other teen demographics
Helical foldamers as selective G-quadruplex ligands
Authors: Koenig Alexander , Laffile Vincent , Thore Stephane , Mackereth Cameron D , Yatsunyk Liliya , Ferrand Yann , Largy Eric , Gabelica Valerie
Published: February 2025

We investigated the G-quadruplex binding selectivity of short aromatic oligoamide helical foldamers comprising quinoline (Q) and pyridine (P) units. We found that the foldamers prefer parallel G-quadruplex structures, especially when the external G-tetrads are sterically accessible. A crystal structure of the tetramer QQPQ with the parallel G-quadruplex formed by dTGGGTTGGGTTGGGTTGGGT shows two quinoline subunits interacting with an external G-tetrad through pi-stacking, and solution NMR confirms that the foldamer targets the 3' and 5' ends of this G-quadruplex. Foldamers can also selectively target sequence variants of the telomeric sequences containing adenine-to-thymine mutation in the loops. The conformational selectivity of foldamers originates from the bulkiness of oligomers with four or more subunits, which imposes steric restrictions on G-quadruplex binding. The flexibility provided by the pyridine subunits was also key to improve affinity. Mixed quinoline-pyridine foldamers are thus a promising class of selective G-quadruplex ligands, and their unique modular scaffold offers new avenues to further improve their affinity and selectivity.
The daily life of a hummingbird: High-throughput tracking shows a spectrum of feeding and movement strategies
Authors: Falk Jay Jinsing , Sargent Alyssa J. , Medina-Madrid Jorge L. , Rico-Guevara Alejandro
Published: February 2025

Most pollinators, with their small size and flight ability, are a challenge to study in the wild, yet their behavior is essential for understanding patterns of biodiversity. For example, hummingbirds play a significant role in their ecosystems—their movements from plant to plant across landscapes ultimately determines their potential as pollinators, but these behaviors are poorly understood. Two movement types are most commonly assumed in hummingbirds: territoriality and traplining, the latter strategy involving repeated and predictable visitation to dispersed feeding locations. However, direct evidence for traplining mostly comes from captive birds. In this study, we collected data from white-necked jacobin hummingbirds (Florisuga mellivora) that were implanted with tiny radio-frequency identification (RFID) tags, tracking their movement among a network of 20 tag-detecting feeders spread across the town of Gamboa, Panamá, for 99 days. The resulting data cover over 47,000 feeder visits from 97 freely moving birds. Overall, we found scant evidence for traplining as a consistent strategy in this species. Instead, we identify three clusters of daily movement types, two of which are difficult to characterize as either territoriality or traplining. Our findings demonstrate that a diversity of movement strategies can be found within a single hummingbird species and even within individuals, and that many questions remain about the movement of these ecologically key vertebrates. To better understand the ecological role of hummingbirds, the description of a greater diversity of movement types beyond territoriality and traplining is likely to be necessary.
Genetically-Determined Low-density Lipoprotein in Ischemic Stroke Survivors
Authors: Wu Kane , Huo Shufan , Rivier Cyprien A , Torres-Lopez Victor , Sharma Richa , de Havenon Adam , Worrall Bradford B , Sheth Kevin N , Falcone Guido J.
Published: February 2025

Background and Objectives: Polygenic susceptibility to hypertension and diabetes negatively impacts the clinical trajectory of ischemic stroke survivors. We hypothesize that polygenic susceptibility to hyperlipidemia (PSH) negatively impacts cholesterol control in this same population. Methods: We conducted a genetic association study using data from the Vitamin Intervention Stroke Prevention (VISP) study, a clinical trial that enrolled survivors of ischemic stroke. PSH was modeled through a polygenic risk score built with 38 independent genetic risk variants for LDL-c that was divided into <20, 20-80, and >80 percentile categories labeled as low, intermediate and high PSH. We used multivariable linear, logistic and Cox regression, as appropriate, to test whether high PSH was associated with risk of uncontrolled hyperlipidemia (LDL-c > 100mg/dl), resistant hyperlipidemia (LDL-c > 100mg/dl despite statin treatment) and clinical outcomes. We replicated our findings in a cohort of ischemic stroke survivors enrolled in the UK Biobank. Results: 1,567 ischemic stroke survivors (mean age 68 years, 35% female) enrolled in VISP were included in the study. Stroke survivors with higher versus low PSH had 66% higher risk of uncontrolled hyperlipidemia (OR 1.66, 95%CI 1.17-2.36), 83% higher risk of resistant hyperlipidemia (1.83, 95%CI 1.00-3.37), twice the risk of recurrent stroke (HR 2.03, 95%CI 1.14-3.61) and 80% higher risk of acute coronary events (HR 1.81, 95%CI 1.18-2.78). The association between high PSH and higher risk of uncontrolled and resistant hyperlipidemia were replicated in 1,634 stroke survivors (mean age 61, 32% female sex) enrolled in the UK Biobank (OR 2.34, 95%CI 1.68-3.28 and OR 2.33, 95%CI 1.61-3.38, respectively). Discussion: Among acute ischemic stroke survivors, higher PSH is associated with worse lipid control and higher risk of recurrent vascular events. Combined with existing evidence on the role of adverse genetic profiles in blood pressure and blood control in this population, our findings support the comprehensive evaluation of polygenic profiles as a cause of failed risk factor control in stroke survivors.
Kinetics of vibriocidal antibody responses among cholera patients in Goma, the Democratic Republic of Congo
Authors: Davis Kilee L. , Nieznanski Carmen , Maisha Felicien , Brintz Ben J. , Clutter Christy , Alam Meer , Saleem Cyrus , Ali Afsar , Morris J. Glenn , Leung Daniel T.
Published: February 2025

Cholera is a diarrheal disease that continues to burden vulnerable populations globally, primarily due to lack of clean water, optimal sanitation and adequate health infrastructure. Understanding the kinetics of antibody responses elicited by toxigenic Vibrio cholerae infection can inform the Sero-epidemiological estimation of disease burden and impact of vaccination efforts. While antibody kinetics have been well-described in South Asia, such studies based in Africa are lacking, despite the ongoing prevalence of cholera in that region. We enrolled stool culture-positive cholera patients admitted to cholera treatment centers in Goma, Democratic Republic of Congo (DRC) between August 2020 and October 2023. Blood samples were collected upon enrollment and during follow-up home visits. We performed vibriocidal assays against V. cholerae O1 Inaba and Ogawa on 212 serum samples from 116 patients, 101 of whom had serotype information available (53% Male; 62% Female, Median age 8 (IQR 4-18). Vibriocidal antibody responses peaked between day 7 and 40 post symptom onset and then waned, with nearly all samples declining to a titer of 320 or lower by day 90, and 160 or lower by day 180. We used a Bayesian exponential decay model to show that there is an approximately 88% probability of a slower decay in participants over 5 years of age compared to younger aged subjects. Our findings corroborate the findings of prior studies conducted in hyperendemic areas in South Asia and provide critical data to inform the timing of vaccination campaigns and interpretation of serosurveillance results in African populations.
The ribosomal protein RPS6A modulates auxin signalling and root development in Arabidopsis
Authors: Pan Kai , Hou Kai , Kong Mengjuan , Tan Shutang
Published: February 2025

Protein biosynthesis by the ribosome is a fundamental biological process in living systems. Recent studies suggest that ribosomal subunits also play essential roles in cell growth and differentiation beyond their roles in protein translation. The ribosomal subunit RPS6 has been studied for more than 50 years in various organisms, but little is known about its specific roles in a certain signalling pathway. In this study, we focused on the functions of Arabidopsis RPS6A in auxin-related root growth and development. The rps6a mutant exhibited a series of auxin-deficient phenotypes, such as shortened primary root length, reduced lateral root number, and defective vasculatures. Treatment of the rps6a mutant with various concentrations of auxin and its analogues did not restore the root defect phenotype, suggesting a defect in the auxin signalling pathway. Further cell biological and global transcriptome analyses revealed that auxin signalling was weakened in the rps6a mutant and that there was a reduced abundance of PIN-FORMED (PIN) auxin transporters. Our work provides insights into the role of the protein biosynthesis pathway involved in auxin signalling.
Enhancing plant broad-spectrum resistance through engineered pattern recognition receptors
Authors: Yang Yuankun , Steidele Christina E. , Loeffelhardt Birgit , Huang Lili , Nuernberger Thorsten , Ding Pingtao , Gust Andrea A.
Published: February 2025

Conventional plant resistance breeding has primarily focused on intracellular immune receptors, while cell-surface pattern recognition receptors (PRRs) have been underexplored due to their comparatively modest contributions to resistance. However, PRRs offer significant untapped potential for crop improvement. In this study, we demonstrate that the Arabidopsis receptor-like protein RLP23, which recognizes molecular patterns from three distinct microbial kingdoms, confers broad-spectrum resistance when introduced into the Solanaceae crop tomato. We also identify the intracellular (IC) domain of RLP23 as crucial for ensuring compatibility and efficacy during heterologous expression. Targeted engineering of the IC domain significantly enhances RLP23 potential utility, enabling transfer of robust resistance against bacterial, fungal, and oomycete pathogens to other plants without compromising yield. We extended this RLP engineering strategy to rice and poplar, highlighting its broad applicability. These findings establish a versatile framework for PRR-based engineering, opening new avenues for sustainable crop protection.
Arabidopsis thaliana Iron Superoxide Dismutase FeSOD1 Protects ARGONAUTE 1 in a Copper-Dependent Manner
Authors: Tomassi Ariel Hernán , Perea-García Ana , Rodrigo Guillermo A , Sanchez-Vicente Javier , Cisneros Adriana E , Olmos Marta , Andrés-Bordería Amparo , López-Dolz Lucio , Daròs José-Antonio , Penarrubia Lola , Carbonell Alberto
Published: February 2025

Copper (Cu) deficiency compromises plant growth and limits crop production. Plants respond to Cu scarcity by activating the expression of several microRNAs, known as Cu-miRNAs, which degrade mRNAs from various cuproproteins to conserve Cu. Cu-miRNAs, like most plant miRNAs, associate with ARGONAUTE 1 (AGO1), the primary effector protein of miRNA-mediated gene silencing pathways, whose function is typically modulated by interacting proteins acting as cofactors. However, how AGO1 is regulated and functions under Cu deficiency remains unknown. Here, we searched for AGO1 interactors in Arabidopsis thaliana plants expressing a functional AGO1 protein tagged with the Twin-Strep-tag (TST) polypeptide, grown under Cu-sufficient or Cu-deficient conditions. TST-AGO1 complexes were affinity-purified, and proteins were identified using tandem mass spectrometry. Interestingly, the iron superoxide dismutase 1 (FeSOD1) encoded by FSD1, was enriched in TST-AGO1 complexes purified from plants grown under Cu deficiency. Moreover, fsd1-2 mutant plants showed reduced levels of AGO1 compared to wild-type plants under Cu sufficiency, while both Cu-miRNA-specific and general AGO1 target mRNAs accumulated to higher levels in fsd1-2 plants under both Cu-deficient and Cu-sufficient conditions compared to wild-type plants. These findings suggest that FeSOD1 is essential for proper AGO1 function, and that its superoxide dismutase activity, which mitigates oxidative stress, enhances AGO1 stability, particularly under Cu deficiency.
Nanometer condensate organization in live cells derived from partitioning measurements
Authors: Dollinger Christina , Potolitsyna Evdokiia , Martin Abigail G , Anand Archish , Datar Gandhar K , Schmit Jeremy D , Riback Joshua A
Published: February 2025

Biomolecules associate, forming condensates that house essential biochemical processes, including ribosome biogenesis. Unraveling how condensates shape macromolecular assembly and transport requires cellular measurements of nanoscale structure. Here, we determine the organization around and between specific proteins at nanometer resolution within condensates, deploying thermodynamic principles to interpret partitioning measurements of designed protein probes. When applied to the nucleolus as a proof of principle, the data reveals considerable inhomogeneity, deviating from that expected within a liquid-like phase. The inhomogeneity can be attributed to ribosome biogenesis, with the local meshwork weakening as biogenesis progresses, facilitating transport. Beyond introducing an innovative modality for biophysical interrogation, our results suggest condensates are far from uniform, simple liquids, a property we conjecture enables regulation and proofreading.
The effect of bivalent HPV vaccination against invasive cervical cancer and CIN3+ in the Netherlands: a national linkage study
Authors: Middeldorp Marit , Brouwer Jesca G.M. , Duijster Janneke W. , Knol Mirjam J. , van Kemenade Folkert J. , Siebers Albert G. , Berkhof Johannes , de Melker Hester E.
Published: February 2025

BackgroundThe protective effect of HPV vaccination against cervical cancer has been demonstrated in registry linkage studies. The start age of screening in those studies was lower than 25 years. We estimated the vaccine effectiveness of bivalent HPV16/18 vaccination against invasive cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3+) in the Netherlands where routine screening starts at age 30 years.MethodsWe linked the vaccination status of women born in year 1993 who were eligible for HPV vaccination at age 16 years with histopathological results recorded in the nationwide pathology databank (Palga). Cumulative risks of invasive cervical cancer and CIN3+ were estimated for fully vaccinated (3 doses or 2 doses ≥ 150 days apart), partially vaccinated, and unvaccinated women. Vaccine effectiveness estimates were adjusted for differences in screening participation between the vaccine groups.FindingsA total of 103,059 women were included, of whom 47,130 were fully vaccinated, 5,098 were partially vaccinated, and 50,831 were unvaccinated. Five (0.011%) cancers were observed in fully vaccinated, two (0.039%) in partially vaccinated, and 42 (0.083%) in unvaccinated women. The vaccine effectiveness in fully vaccinated women was 91.5% (95% CI 78.9, 96.6) against cancer and 81.2% (95% CI 78.4, 83.7) against CIN3+. The vaccine effectiveness in partially vaccinated women was 48.1% (95% CI -56.8, 82.8) against cancer and 58.4% (95% CI 45.3, 68.3) against CIN3+.InterpretationThe high effectiveness of bivalent HPV vaccination against cervical cancer and CIN3+ and the low cancer incidence supports a screening start age of 30 years in vaccinated women.
Exploring Zero-Shot Cross-Lingual Biomedical Concept Normalization via Large Language Models
Authors: Rouhizadeh Hossein , Yazdani Anthony , Zhang Boya , Teodoro Douglas
Published: February 2025

Over the past few years, discriminative and generative large language models (LLMs) have emerged as the predominant approaches in natural language processing. However, despite significant advancements, there remains a gap in comparing the performance of discriminative and generative LLMs in cross-lingual biomedical concept normalization. In this paper, we perform a comparative study across several LLMs on the challenging task of cross-lingual biomedical concept normalization via dense retrieval. We utilize the XL-BEL dataset covering 10 languages to evaluate the model's capacity to generalize across various linguistic contexts without further adaptation. The experimental findings demonstrate that e5, a discriminative model, exhibited superior performance, whereas BioMistral emerged as the top-performing generative LLM. The code for reproducing the experiments is available at: https://github.com/hrouhizadeh/zsh_cl_bcn.
CombiCTx: Screening diffusion gradients of anti-cancer drug combinations
Authors: Stelzl Christina , Lerma-Clavero Ada , Camenisch Selina , Simon Benoit , Eriksson Olle , Degerstedt Oliver , Lennernäs Hans , Heindryckx Femke , Kreuger Johan , O'Callaghan Paul
Published: February 2025

The reduced effectiveness of chemotherapy in many patients highlights the need for novel drug combinations and optimal ratios that target multiple survival mechanisms, which tumors may engage to confer drug resistance. Dynamic conditions within the tumor microenvironment shape cell behavior and influence the response to anti-cancer drugs, varying by cell type and local context. Accordingly, assays that identify effective concentrations and drug interactions (additive, synergistic, or antagonistic) in a relevant tumor tissue model are required to discover new combination treatments. To address this need for combinatorial chemotherapeutic (CTx) screening assays, we reconfigured CombiANT, a device for testing antibiotic interactions, and present a new assay called CombiCTx. The assay uses a device with three reservoirs containing gels loaded with chemotherapeutics or other anti-cancer drugs. The drug-loaded device is inverted and placed in a standard culture dish containing cancer cells, and both are then enclosed in gel. As drugs diffuse from the reservoirs, cancer cells are exposed to overlapping dynamic gradients of anti-cancer drugs, which can interact in various ways. We imaged doxorubicin diffusion in the assay using timelapse microscopy and employed the apoptotic agent staurosporine as a model drug, and established an imaging protocol for quantifying MDA-MB-231 breast cancer cell apoptosis along drug diffusion gradients. Finally, we tested navitoclax and gemcitabine to demonstrate the capacity of CombiCTx to evaluate combined cytotoxic effects while accounting for drug diffusion. Evaluating drug combinations with an assay that accounts for drug properties that influence diffusion in a complex tumor matrix may provide clinically relevant information.
Cortical Excitability during Fixations Drives Frequency-Specific Neural Activity in Children and Adults
Authors: Marriott Haresign Ira , Charman Tony , Johnson Mark H , Mason Luke , Bazelmans Tessel , Begum-Ali Jannath , Jones Emily J.H , Wass Sam V
Published: February 2025

Extensive previous research has examined how neuronal oscillations support basic cognitive processes, from early development into adulthood. However, the question of how these oscillations originate and are maintained remains relatively underexplored. Here, we examine how transient increases in cortical excitability that occur time-locked to the offsets of spontaneous eye movements associate with frequency-specific neural activity, and how these relationships change over development and between contexts (social vs non-social). We examine two datasets of combined EEG and eye-tracking data from 24-month-old children (N=114) and adults (N=108) while they watched stimuli that were either social (an actor singing nursery rhythms) or non-social (dynamic toys). EEG data was time-locked to the offsets of eye movements and analysed using a spectrum of methods designed to highlight the progression of various neural signals across time, frequency, and space (topography). Fixation-related potentials (FRPs) manifest as a differentiable combination of eye movement-related artifact and genuine neural activity. Child FRPs are slower and unfold over longer time periods, which manifests as differences in the frequency domain. Even after removing artifact, dipoles associated with fixation-related P1 and N170 components manifest as Theta activity over fronto-central areas, along with activity in other frequencies, in children but not adults. Data sections where no fixation-related potentials are present show strongly attenuated oscillatory activity. Our results show that a variety of previously documented developmental effects in the frequency domain may be better understood as fine-grained, movement-induced brain states.
Molecular determinants of cardiac lymphatic dysfunction in a chronic pressure-overload model
Authors: Heron Coraline , Lemarcis Theo , Laguerre Oceane , Bourgeois Benjamin , Thuilliez Corentin , Valentin Chloe LA , Dumesnil Anais , Valet Manon , Godefroy David , Schapman Damien , Riou Gaetan , Candon Sophie , Derambure Celine , Zernecke Alma , Berard Caroline , Dauchel Helene , Tardif Virginie , Brakenhielm Ebba
Published: February 2025

Cardiac lymphatics have emerged as potential targets in cardiovascular diseases (CVDs). However, we recently reported that despite extensive lymphatic expansion during experimental cardiac pressure-overload, lymphatic drainage remained insufficient. To unravel the cellular and molecular mechanisms underlying lymphatic dysfunction in CVDs, we applied cardiac single-cell (sc) analyses in a murine heart failure model. Transaortic constriction (TAC), in C57BL/6J and BALB/c mice, was used to model chronic pressure-overload-induced cardiac hypertrophy and heart failure, respectively. Cardiac lymphatic (LEC) and blood vascular (BECs) endothelial cells were analyzed by scRNAseq (10XGenomics). Lymphatic targets were validated by immunohistochemistry and wholemount-imaging, and in vitro using human LEC cultures. We identified three distinct cardiac lymphatic subpopulations, capillary (LEC1), precollector (LEC2), and valvular (LEC3) clusters, and several BECs clusters, including venous BEC (vBEC). Chronic pressure-overload led to expansion of lymphatic capillaries and loss of valves in BALB/c, but not C75BL6/J. Analysis of differentially expressed genes (DEG) post-TAC revealed reduction only in BALB/c of lymphatic cell-junction components. In contrast, LEC expression of anchoring filaments, immune cell-adhesion molecules, and chemokines was preserved, or increased, indicating functional lymphatic-mediated immune cell uptake post-TAC. Interestingly, around 35% of DEGs identified in cardiac LECs post-TAC were similarly altered in interleukin (IL)-1β-stimulated human LECs. In conclusion, loss of lymphatic valves and dysregulated lymphatic barrier properties may underly poor drainage capacity during pressure-overload, despite potent lymphangiogenesis and preserved LEC immune attraction. Further studies are needed to address how to restore lymphatic health to accelerate resolution of both inflammation and edema in CVDs.
The hidden prevalence and unique protein folds of huge phages
Authors: Chen LinXing
Published: February 2025

Huge phages are remarkable for their expansive genomes (≥200 kbp, and up to 841 kbp to date), global distribution, and intricate functional repertoires. However, their study has been hindered by challenges in genome identification and the lack of a comprehensive reference database. Using vRep, we established the Huge Phage Genome Collection (HPGC), a curated resource of 7,295 non-redundant huge phage genomes spanning 4,613 species-level groups. Within HPGC, we identified an overlooked and prevalent clade, HP8026, which constitutes ~1.2% of human gut metagenomic reads, suggesting its potential in fecal contamination monitoring and a promissing modulator of gut microbiome dynamics. Complementing HPGC, we developed the Huge Phage Protein Structure Database (HPDB), which catalogs 15,594 structure clusters derived from 589,960 predicted proteomes. Notably, 40% of these clusters presented in huge phages only, exhibit specific protein folds. Additionally, 3% of the HPDB clusters were absent in other viral forms, including the plasmid-originated ArdC that could protect huge phages from the antiviral mechanisms of their hosts. Collectively, HPGC and HPDB provide a pioneering framework for exploring the evolution, functional innovation, and biotechnological potential of huge phages, while serving as indispensable references for viral ecology and structural biology.
Dysregulation of replication stress-induced ROS in transformed cell lines: a vicious circle at cancer initiation
Authors: Ragu Sandrine , Dardillac Elodie , Caillat Sylvain , Ravanat Jean-Luc , Lopez Bernard S.
Published: February 2025

The canonical DNA damage response (DDR) maintains genome stability, involving DNA synthesis/cell cycle arrest. However, unchallenged cells proliferate when they are continually exposed to low-level/endogenous replication stress. We previously discovered and characterized a noncanonical cellular response that is specific to nonblocking replication stress, i.e., low-level stress (LoL-DDR), in primary cells. Although this response generates replication stress-induced reactive oxygen species (RIR), it triggers a program that prevents the accumulation of premutagenic 8-oxo-guanine (8-oxoG). Primary cells control RIR production via NADPH oxidases. Increasing the severity of replication stress above a precise threshold triggers the canonical DDR, leading to cell cycle arrest and RIR suppression, resulting in a peak-shaped dose response for RIR production. Here, we show that the LoL-DDR is dysregulated in cancer cell lines, which exhibit the following differences compared with primary cells: 1- RIR are not detoxified under high-level stress conditions, resulting in a continuous increase in the dose-response curve of RIR production; 2- RIR are not produced by NADPH oxidases; and 3- replication stress favors the accumulation of the premutagenic 8-oxoG. Moreover, using an in vitro breast cancer progression model, we show that LoL-DDR dysregulation occurs at an early stage of cancer progression. Since, conversely, ROS trigger replication stress this establishes a vicious circle involving replication-stress and ROS that continuously jeopardizes genome integrity that should fuel and amplify tumorigenesis.
Immunization with peptide encapsulated within synthetic spores activates T cell responses and reduces tumor growth
Authors: D'Atri Domenico , Tondini Elena , Machinandiarena Federico , Kong Minsuk , Mia Alilin , Gallardo Devorah , Tanner Kandice , Hewitt Stephen , Fitzgerald David J , Ramamurthi Kumaran S
Published: February 2025

Peptide-based therapeutic immunizations represent safe approaches to elicit antigen-specific T cell responses, but their broad utility remains limited due to poor immunogenicity and short in vivo stability due to rapid degradation and clearance. Here we employed synthetic bacterial spore-like particles, "SSHELs", made entirely of biocompatible materials, to deliver a model peptide antigen in the absence of additional adjuvants. SSHELs carrying the peptide antigen were internalized by dendritic cells and SSHEL-delivered peptides were then processed and cross-presented in vitro and in vivo more efficiently than free peptides. Further, SSHEL-delivered peptides elicited effective antigen-specific T cell expansion in a manner that was dependent on particle size and peptide presentation mode (encased peptides were superior to surface-attached peptides). In a mouse melanoma model expressing the antigen ovalbumin, therapeutic immunization reduced tumor size and increased survival. We propose that SSHELs are a self-adjuvanting peptide delivery system that mimics a natural presentation to elicit a robust immune response.
Keratin 15 promotes a progenitor cell state in basal keratinocytes of skin epidermis
Authors: Redmond Catherine J. , Steiner Sarah N. , Cohen Erez , Johnson Craig N. , Özlü Nurhan , Coulombe Pierre A.
Published: February 2025

The type I intermediate filament proteins keratin 14 (K14) and keratin 15 (K15) are common to all complex epithelia. K14 is highly expressed by progenitor keratinocytes, in which it provides essential mechanical integrity and gates keratinocyte entry into differentiation by sequestering YAP1, a transcriptional effector of Hippo signaling, to the cytoplasm. K15 has long been used as a marker of hair bulge stem cells though its specific role in skin epithelia is unknown. Here we show that the lack of two biochemical determinants, a cysteine residue within the stutter motif of the central rod domain and a 14-3-3 binding site in the N-terminal head domain, renders K15 unable to effectively sequester YAP1 in the cytoplasm. We combine insight obtained from cell culture and transgenic mouse models with computational analyses of transcriptomics data and propose a model in which the K15:K14 ratio promotes a progenitor state and antagonizes differentiation in keratinocytes of the epidermis.
Does financial experience of women owners of micro businesses promote microfinance lending and their continued existence in rural Uganda?
Authors: Okello Candiya Bongomin George , Semukono Frederick , Baleke Yiga Lubega Joseph , Yourougou Pierre
Published: February 2025

Purpose

Financial experience is very important in today’s dynamic world of constant globalization with the upsurge in sophisticated financial products entering the financial markets, especially in developing countries. This is because it helps the illiterate unbanked poor women owners of micro businesses to make wise financial judgments and options guided by psychology and cognition. This paper aims to ascertain how financial experience can promote microfinance lending and the continued existence of women micro businesses in rural Uganda through an intervening role.

Design/methodology/approach

The paper employs a structural equation model through SmartPLS software to ascertain how financial experience can promote microfinance lending and the continued existence of women micro businesses in rural Uganda through an intervening role.

Findings

The empirical findings from this study indicated that financial experience, as a significant and positive mediator, improves microfinance lending and the continued existence of women micro businesses in rural Uganda.

Research limitations/implications

Owing to the geographical ambit of the current study and sample source from only one developing country, future studies may collect data from other regions of the world for comparative analysis to give more insights on the role of financial experience in rural financial markets.

Practical implications

The government of Uganda should promote financial literacy to enhance the financial experience of women owners of micro businesses to help them make better financial judgements in the rural financial markets. This may increase microfinance lending and the continued existence of vibrant women micro businesses in rural areas. As a result, this could lead to the creation of more jobs for the ever-growing younger population in Uganda.

Originality/value

This study is motivated by the lack of understanding and experience about key financial concepts among more than 3.5 billion adults, mostly women. It applies the Experiential Learning Theory grounded in psychology and cognition to show how the financial experience of women who run micro businesses derived from repeated retrieval of knowledge and reflection, can help them to make sound financial judgments to become financially included by rural-based microfinance institutions. Learning-by-doing allows women owners of micro businesses to repetitively take prudent saving, borrowing and investment selections that help them to generate income to meet timely loan repayment to access more microcredit for the continued existence. This is inadequate in the current theory of microfinance lending in rural financial markets.
Customer sustainability perception: a scale development study for food products
Authors: Panda Rajesh , Swar Biranchi Narayan
Published: February 2025

Purpose

With increasing consumer awareness about sustainability, there is a notable shift towards sustainable consumption. This study investigates branded food products and consumer perceptions of sustainability in India, aiming to understand how consumers perceive sustainability. The research proposes and validates the customer sustainability perception (CSP) scale, which includes four dimensions: marketing communication, experiential dimension, product attributes and social media information.

Design/methodology/approach

Employing rigorous data analysis techniques, the study uses exploratory factor analysis (EFA) to uncover latent factors and confirmatory factor analysis (CFA) to validate the structure and reliability of the CSP scale across two samples. These methods ensure the robustness and reliability of the proposed framework.

Findings

The findings validate the CSP scale, revealing that consumer perceptions of sustainability are influenced by marketing communication, product attributes, experiential dimensions and social media information. The empirical validation of the CSP framework offers practical insights for businesses to enhance their sustainability strategies and effectively communicate with environmentally conscious consumers.

Practical implications

Businesses can leverage these insights to enhance their sustainability strategies and communicate eco-friendly initiatives effectively. This robust foundation supports future studies and practical applications in sustainable marketing.

Originality/value

This research advances theoretical understanding by integrating diverse dimensions of consumer perceptions into a cohesive framework. The CSP scale provides a comprehensive tool for measuring consumer sustainability perceptions and elucidates the interrelationships between various factors influencing consumer behaviour.
Digital markets: formative components, regulation, challenges and insights from the European Union Digital Markets Act
Authors: Ozili Peterson
Published: February 2025

Purpose

This study aims to examine digital markets, their formative components, regulation and challenges. It also presents a concise definition of “digital markets” and suggests a link between digital markets and digital financial inclusion.

Design/methodology/approach

This study adopts a conceptual discussion of digital markets, their formative components and regulation.

Findings

The study projects digital markets to be a game changer for society. It analyses the regulation of digital markets, particularly the recent European Union Digital Markets Act, and show that regulation focus mostly on large technological companies. The study also shows the benefits of digital market regulation for users of digital markets and the demerits for the large technological companies who own the world’s largest digital transactional platforms in digital markets. The criticisms of regulating large technological companies are also identified.

Originality/value

There has been very little policy or academic discussion or debate about the value of digital markets in the literature. Most debates in the literature focus on the large technological companies that operate in digital markets, but there are no discussions or debates in the literature about the value proposition of digital markets as a standalone concept.
Research data management and FAIR compliance through popular research data repositories: an exploratory study
Authors: Bhardwaj Raj Kumar , Nazim Mohammad , Verma Manoj Kumar
Published: February 2025

Purpose

The present study examines the features and services of four research data repositories (RDRs): Dataverse, Dryad, Zenodo and Figshare. The study explores whether these RDRs adhere to the FAIR principles and suggests the features and services that need to be added to enhance their functionality.

Design/methodology/approach

An online survey was conducted to identify the features of four popular RDRs. The study evaluates the features of four popular RDRs using the specially designed checklist method based on FAIR principles. The checklist is based on 11 construct progressions used to evaluate the features and services of four popular RDRs. The final checklist contains 11 constructs with 199 check spots.

Findings

Figshare has attained the highest features for findability, accessibility, interoperability and reusability. It is identified that Figshare, with 116 (58.3%) scored the highest points and ranked no 1. It has also been found that Figshare recorded the highest features in 6 constructs out of the 11. Dataverse, with 90 (45.2%) features, ranked 2nd; Zenodo, with 86 (43.2%), ranked 3rd. The lowest features are found in Dryad, with 85 (42.7%). Furthermore, the study found that all four popular RDRs have poor features relating to “research data access metrics” features 23.3%, “output, data license and other advanced features” 22.6%. The very less features recorded in the category “services in RDRs” are 15.9%. Therefore, the features of these three constructs framed under FAIR need to be upgraded to improve the functionalities of the four popular RDRs.

Practical implications

The findings of the study are useful for researchers in choosing the appropriate RDR for accessing and sharing data and can be used by data scientists, librarians and policymakers in starting the research data management services in academic and research institutions. Furthermore, the study can also help impart research data literacy instructions to researchers and faculty members.

Originality/value

This study has prepared a special checklist based on FAIR principles to evaluate the features and services of RDRs. No prior study has been conducted to explore the features of popular RDRs and their compliance with FAIR principles based on the checklist method.
Achieving fashion sustainability: circular economy enablers and the theory of planned behavior
Authors: Singh Garima , Kumar Ashwani
Published: February 2025

Purpose

This study aims to propose an extended model of the theory of planned behavior (TPB) in the fashion industry. This model helps to identify key enablers for consumers, which will facilitate the adoption of a circular economy (CE). These enablers were identified through extensive literature review.

Design/methodology/approach

An online survey was conducted with 362 respondents to test the model in the fashion industry. Convenience sampling was used and the survey was distributed via social media and email. Data analysis was performed using partial least squares and structural equation modeling was used to explore the relationships among the variables.

Findings

The findings indicate a positive and significant relationship between consumers’ environmental knowledge and their attitudes toward adopting the CE model. In addition, the results demonstrate that providing consumers with a channel to return used clothing positively influences their attitude. The availability of such a channel significantly impacts consumer attitudes toward CE.

Originality/value

This study contributes three novel elements to the TPB framework: availability, environmental knowledge and monetary benefits. This finding posits that consumers’ attitudes toward CE are significantly influenced by their environmental knowledge. This study also highlighted that attitude acts as a mediator in the relationship between environmental knowledge and intention, as well as between availability and intention.