bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Phylogeny and the Evolution of Parasitic Strategies in Trematoda
Authors: Xiang Chuan-Yu , Jakovlić Ivan , Ye Tong , Song Rui , Zou Hong , Wang Gui-Tang , Li Wen-Xiang , Zhang Dong 
Published: August 2024

AbstractTrematodes are obligatory parasites that generally must transmit between hosts to complete their life cycle. They parasitize varying numbers of intermediate hosts (0, 1 or 2), but the evolutionary history of these strategies and the ancestral states remain unknown. We conducted the ancestral state reconstruction of the number of intermediate hosts using mitogenomic (Trematoda) and nuclear-genomic (Neodermata) topologies. Aspidogastrea was identified as the sister-group (“basal”) to all other Trematoda using a range of approaches, so it is crucial for studying the evolutionary history of trematodes. However, there is only one transcriptome available for this lineage, and mitochondrial genomes (mitogenomes) remain unavailable. Herein, we sequenced mitogenomes of two aspidogastreans:Aspidogaster ijimaiandAspidogaster conchicola. As the ancestral state reconstruction analysis is topology-sensitive, we tested multiple phylogenetic strategies, comprising the outgroup selection, phylogenetic models, partitioning strategies, and topological constraints. These mitogenomic phylogenies exhibited pronounced topological instability, with Aspidogastrea resolved as the “basal” radiation in most, but not all, topologies. Based on our analyses, Cestoda was the optimal outgroup choice, and the “heterogeneous” CAT-GTR model in PhyloBayes was the optimal model choice. We inferred the time tree and conducted ancestral state reconstruction analyses using this “optimal” topology, as well as constrained mitogenomic and nuclear genomic topologies. Results were ambiguous for some lineages, but scenario that received the strongest support is the direct life cycle (no intermediate hosts) in the ancestors of Trematoda (proto-trematodes) and Aspidogastrea (proto-aspidogastreans), while the ancestor of Digenea (proto-digeneans) had two intermediate hosts. The inferred scenario indicates that host strategies are relatively plastic among trematodes, putatively comprising several independent host gains, and multiple host losses. We propose a timeline for these events and discuss the role that alternating sexual and asexual generations putatively played in the evolution of complex parasitic life histories in digeneans.
Confidence and insight into working memories are shaped by attention and recent performance
Authors: Chekroud Sammi R , Nobre Anna C , Kolling Nils 
Published: August 2024

AbstractWorking memory (WM) is capacity-limited, and our ability to access information from WM is variable, but selective attention to working memory contents can improve performance. People are able to make introspective judgements regarding the quality of their memories, and these judgements are linked to objective memory performance. However, it remains unknown whether benefits of internally directed attention on memory performance occur alongside commensurate changes in introspective judgments. Across two experiments, we used retrospective cues (retro-cues) during working-memory maintenance to direct attention to items in memory. We then examined their consequence on introspective judgements. In the second experiment, we provided trial-wise feedback on performance. We found that selective attention improved confidence judgements and not just performance of the probed item. We were also able to judge participants’ genuine insight into working-memory contents through the correlation between confidence judgements and memory quality. Neurophysiologically, alpha desynchronization correlated first with memory error and then confidence during retro-cueing, suggesting a sequential process of attentional enhancement of memory contents and introspective insight. Further, we showed that participants can use feedback on the accuracy of confidence judgements to update their beliefs across time, according to performance. Our results emphasize flexibility in working memory by showing we can selectively modulate our confidence about its contents based on internally directed attention or objective feedback.
Intra-cluster receptor density (IRD) dictates TNFR1 clusters’ signaling efficacy
Authors: Jana Subhamoy , Roy Priyanka , Das Jibitesh , Biswas Parijat , Nanda Nandana , Sinha Bidisha , Sinha Deepak Kumar 
Published: August 2024

AbstractTumor Necrosis Factor Receptor 1 (TNFR1) signaling determines cell fate during inflammation, immunopathogenesis, and tumorigenesis. TNFR1 proteins homo-oligomerize into clusters on the plasma membrane. The potential impact of TNFR1 clustering on downstream signaling remains unexplored. Homo-FRET measurements elucidate that alterations in intra-cluster receptor density (IRD) dictate the outcomes of downstream TNFR1 signaling. Soluble TNF-α (sTNF-α) elevates IRD within the TNFR1 clusters’ core while diminishing it in the rim, through intra-cluster dynamic reorganization of TNFR1. Decreasing TNFR1 IRD through increasing membrane tension, administering TNFR1 antagonist zafirlukast, actin depolymerization, or depleting cholesterol impedes sTNF-α-mediated stimulation. Conversely, increasing IRD by reducing membrane tension or exposing cells to 3D gel-like microenvironment induces ligand-independent TNFR1 signaling. These findings suggest a broader applicability of IRD in modulating signaling pathways across other receptor families, offering insights for innovative strategies in TNFR1 signaling modulation.
New tools to monitorPseudomonas aeruginosainfection and biofilmsin vivoinC. elegans
Authors: Ragno Martina , Xue Feng , Blackburn Sarah A. , Fasseas Michael , Maitra Sushmita , Tholozan Frederique , Thompson Rachel , Sellars Laura , Hall Rebecca , Saunter Chris , Weinkove David , Ezcurra Marina 
Published: August 2024

AbstractAntimicrobial resistance is a growing health problem.Pseudomonas aeruginosais a pathogen of major concern because of its multidrug resistance and global threat, especially in health-care settings. The pathogenesis and drug resistance ofP. aeruginosadepends on its ability to form biofilms, making infections chronic and untreatable as the biofilm protects against antibiotics and host immunity. A major barrier to developing new antimicrobials is the lack ofin vivobiofilm models. Standard microbiological testing is usually performedin vitrousing planktonic bacteria, without representation of biofilms, reducing translatability. Here we develop tools to study both infection and biofilm formation byP. aeruginosa in vivoto accelerate development of strategies targeting infection and pathogenic biofilms. Using the nematodeCaenorhabditis elegansandP. aeruginosareporters combined within vivoimaging we show that fluorescentP. aeruginosareporters that form biofilmsin vitrocan be used to visualise tissue infection. Using automated tracking ofC. elegansmovement, we find that that the timing of this infection corresponds with a decline in health endpoints. In a mutant strain ofP. aeruginosalacking RhlR, a transcription factor that controls quorum sensing and biofilm formation, we find reduced capacity ofP. aeruginosato form biofilms, invade host tissues and negatively impact healthspan and survival. Our findings suggest that RhlR could be a new antimicrobial target to reduceP. aeruginosabiofilms and virulencein vivoandC. eleganscould be used to more effectively screen for new drugs to combat antimicrobial resistance.
Uncoupling de novo pyrimidine biosynthesis from mitochondrial electron transport by ectopic expression of cytosolic DHODH
Authors: Curtabbi Andrea , Cortés Rocío Sanz , Enríquez José Antonio 
Published: August 2024

AbstractDihydroorotate dehydrogenase (DHODH) is an enzyme involved in the biosynthesis of pyrimidine nucleotides. In most eukaryotes, this enzyme is bound to the inner mitochondrial membrane, where it couples the synthesis of orotate with the reduction of ubiquinone. As ubiquinone must be regenerated by respiratory complex III, pyrimidine biosynthesis and cellular respiration are tightly coupled. Consequently, inhibition of respiration leads to cessation of DNA synthesis and impairs cell proliferation. We show that expression ofSaccharomyces cerevisiaeURA1 gene (ScURA) in mammalian cells uncouples biosynthesis of pyrimidines from mitochondrial electron transport. ScURA forms a homodimer in the cytosol that uses fumarate instead of ubiquinone as the electron acceptor, enabling oxygen-independent pyrimidine biosynthesis. Cells expressingScURAare resistant to drugs that inhibit complex III and the mitochondrial ribosome. ScURA enables the growth of mtDNA-lacking ρ0cells in uridine-deficient medium and ameliorates the phenotype of cellular models of mitochondrial diseases. This genetic tool uncovers the contribution of pyrimidine biosynthesis to the phenotypes arising from electron transport chain defects.
In-silico identification of archaeal DNA-binding proteins
Authors: Donvil Linus , Housmans Joëlle A.J. , Peeters Eveline , Vranken Wim , Orlando Gabriele 
Published: August 2024

ABSTRACTThe rapid advancement of next-generation sequencing technologies has generated an immense volume of genetic data. However, this data is unevenly distributed, with well-studied organisms being disproportionately represented, while other organisms, such as from archaea, remain significantly underexplored. The study of archaea is particularly challenging due to the extreme environments they inhabit and the difficulties associated with culturing them in the laboratory. Despite these challenges, archaea likely represent a crucial evolutionary link between eukaryotic and prokaryotic organisms, and their investigation could shed light on the early stages of life on Earth. Yet, a significant portion of archaeal proteins are annotated with limited or inaccurate information.Among the various classes of archaeal proteins, DNA-binding proteins are of particular importance. While they represent a large portion of every known proteome, their identification in archaea is complicated by the substantial evolutionary divergence between archaeal and the other better studied organisms.To address the challenges of identifying DNA-binding proteins in archaea, we developed Xenusia, a neural network-based tool capable of screening entire archaeal proteomes to identify DNA-binding proteins. Xenusia has proven effective across diverse datasets, including metagenomics data, successfully identifying novel DNA-binding proteins, with experimental validation of its predictions.Xenusia is available as a PyPI package, with source code accessible athttps://github.com/grogdrinker/xenusia, and as a Google Colab web server application athttps://colab.research.google.com/drive/1c4eb4sEz8OsBqHL62XDFrqmwa7CxImww?usp=sharing.
Infectious subgenomic amplicon strategies for Japanese encephalitis and West Nile viruses
Authors: Singh Prince Pal , Khanh Le Nguyen Phuong , Karniychuk Uladzimir 
Published: August 2024

ABSTRACTClassical methods for constructing infectious cDNA clones of flaviviruses are often hindered by instability and toxicity. The Infectious-Subgenomic-Amplicons (ISA) method is an advancement which utilizes overlapping DNA fragments representing viral genomic sequence and in-cell recombination to bypass bacterial plasmid assembly. However, the ISA method has limitations due to the toxicity of some ISA DNA fragments in bacteria during synthetic production. We validated modified ISA strategies for producing toxic ISA Japanese encephalitis virus (JEV) and West Nile virus (WNV) DNA fragments. Three approaches were explored including subdividing toxic DNA fragments into two sub-fragments for synthetic clonal production, using a low-copy bacterial plasmid, and subdividing the toxic DNA fragments into four short overlapping sub- fragments, each up to 1.8 kb. The latter novel approach in ISA applications enabled the synthesis of entirely bacteria-free ISA DNA fragments. Our results demonstrate that subdividing toxic fragments into sub-fragments smaller than 1.8 kb for synthesis is the efficient strategy, circumventing the need for bacterial plasmids and ensuring rapid production of synthetic flaviviruses. This method also shortens the production timeline. We also compared the efficacy of JEV and WNV ISA in zinc finger antiviral protein 1 (ZAP) wild-type and knockout cells and found that knockout cells may be more effective for ISA rescue of flaviviruses, including attenuated strains for live attenuated vaccines. The validated modified ISA strategies provide an efficient approach for producing synthetic JEV and WNV. This will enable rapid research during outbreaks of emerging flaviviruses by facilitating the quick generation of new virus variants.
Novel Insights into Post-Myocardial Infarction Cardiac Remodeling through Algorithmic Detection of Cell-Type Composition Shifts
Authors: Gural Brian , Kirkland Logan , Hockett Abbey , Sandroni Peyton , Zhang Jiandong , Rosa-Garrido Manuel , Swift Samantha K. , Chapski Douglas , Flinn Michael A , O’Meara Caitlin C , Vondriska Thomas M , Patterson Michaela , Jensen Brian C. , Rau Christoph D 
Published: August 2024

AbstractBackgroundRecent advances in single cell sequencing have led to an increased focus on the role of cell-type composition in phenotypic presentation and disease progression. Cell-type composition research in the heart is challenging due to large, frequently multinucleated cardiomyocytes that preclude most single cell approaches from obtaining accurate measurements of cell composition. Ourin silicostudies reveal that ignoring cell type composition when calculating differentially expressed genes (DEGs) can have significant consequences. For example, a relatively small change in cell abundance of only 10% can result in over 25% of DEGs being false positives.MethodsWe have implemented an algorithmic approach that uses snRNAseq datasets as a reference to accurately calculate cell type compositions from bulk RNAseq datasets through robust data cleaning, gene selection, and multi-sample cross-subject and cross-cell-type deconvolution. We applied our approach to cardiomyocyte-specific α1A adrenergic receptor (CM-α1A-AR) knockout mice. 8-12 week-old mice (either WT or CM-α1A-KO) were subjected to permanent left coronary artery (LCA) ligation or sham surgery (n=4 per group). Transcriptomes from the infarct border zones were collected 3 days later and analyzed using our algorithm to determine cell-type abundances, corrected differential expression calculations using DESeq2, and validated these findings using RNAscope.ResultsUncorrected DEGs for the CM-α1A-KO X LCA interaction term featured many cell-type specific genes such asTimp4(fibroblasts) andAplnr(cardiomyocytes) and overall GO enrichment for terms pertaining to cardiomyocyte differentiation (P=3.1E-4). Using our algorithm, we observe a striking loss of cardiomyocytes and gain in fibroblasts in the α1A-KO + LCA mice that was not recapitulated in WT + LCA animals, although we did observe a similar increase in macrophage abundance in both conditions. This recapitulates prior results that showed a much more severe heart failure phenotype in CM-α1A-KO + LCA mice. Following correction for cell-type, our DEGs now highlight a novel set of genes enriched for GO terms such as cardiac contraction (P=3.7E-5) and actin filament organization (P=6.3E-5).ConclusionsOur algorithm identifies and corrects for cell-type abundance in bulk RNAseq datasets opening new avenues for research on novel genes and pathways as well as an improved understanding of the role of cardiac cell types in cardiovascular disease.
TheToxoplasma gondiihomolog of ATPase inhibitory factor 1 is critical for mitochondrial cristae maintenance and stress response
Authors: Usey Madelaine M. , Ruberto Anthony A. , Huet Diego 
Published: August 2024

ABSTRACTThe production of energy in the form of ATP by the mitochondrial ATP synthase must be tightly controlled. One well-conserved form of regulation is mediated via ATPase inhibitory factor 1 (IF1), which governs ATP synthase activity and gene expression patterns through a cytoprotective process known as mitohormesis. In apicomplexans, the processes regulating ATP synthase activity are not fully elucidated. Using the model apicomplexanToxoplasma gondii, we found that knockout and overexpression of TgIF1, the structural homolog of IF1, significantly affected gene expression. Additionally, TgIF1 overexpression resulted in the formation of a stable TgIF1 oligomer that increased the presence of higher order ATP synthase oligomers. We also show that parasites lacking TgIF1 exhibit reduced mitochondrial cristae density, and that while TgIF1 levels do not affect growth in conventional culture conditions, they are crucial for parasite survival under hypoxia. Interestingly, TgIF1 overexpression enhances recovery from oxidative stress, suggesting a mitohormetic function. In summary, while TgIF1 does not appear to play a role in metabolic regulation under conventional growth conditions, our work highlights its importance for adapting to stressors faced byT. gondiiand other apicomplexans throughout their intricate life cycles.SIGNIFICANCE STATEMENTToxoplasma gondiiis a member of the Apicomplexa, a phylum consisting of parasites responsible for significant global morbidity and mortality. An intact mitochondrial ATP synthase is criticalT. gondiisurvival, but how this enzyme is regulated is not completely understood.Our work demonstrates that theT. gondiihomolog of ATPase inhibitory factor 1 (TgIF1) does not impact metabolism under standard culture conditions, but plays a role in mitochondrial cristae density and stress responses.This study reveals the role of TgIF1 in regulating ATP synthase activity under stressful conditions and increases our understanding of this divergent enzyme inT. gondii.
Development of a Novel Japanese Eel Myoblast Cell Line for Application in Cultured Meat Production
Authors: Ikeda Daisuke , Otsuka Yui , Kan-no Nobuhiro 
Published: August 2024

AbstractThe present study investigates the isolation, analysis, and characterization of primary cultured cells derived from the muscle tissue of Japanese eel (Anguilla japonica), culminating in establishing a spontaneously immortalized myoblast cell line, JEM1129. We isolated satellite cells from eel muscle tissue to establish a foundation for cultured eel meat production. While initial cell cultures contained myoblasts, continued passaging led to a decline in myoblast characteristics and an increase in fibroblast-like cells. RNA-Seq and RT-qPCR analyses showed significant downregulation of well-established markers for satellite cells and myoblasts, such as pax7a and myoD, over successive passages, highlighting a loss of myoblastic traits. Single-cell cloning was employed to overcome this challenge and maintain myoblast purity, leading to the successful creation of the JEM1129 cell line. These JEM1129 cells demonstrated enhanced expression of myoblast marker genes, exceeding the initial primary culture cell population. The cells showed strong myotube formation, particularly when cultured in a differentiation medium, indicating their robust potential for muscle development. The JEM1129 cell line represents a significant advancement in the cultivation of eel muscle cells, offering a promising avenue for cultured meat production. The findings contribute to a deeper understanding of muscle cell biology and provide valuable insights into using fish-derived myoblasts for cultured meat production.HighlightsSingle-cell cloning established a stable Japanese eel myoblast line, JEM1129.Single-cell cloning aids in establishing spontaneously immortalized fish myoblasts.JEM1129 demonstrates robust myogenic differentiation, crucial for cultured meat.Potential for sustainable eel meat production reducing wild eel depletion.
The inattentional rhythm in audition
Authors: Lui Troby Ka-Yan , Boglietti Eva , Zoefel Benedikt 
Published: August 2024

AbstractThe detection of temporally unpredictable visual targets depends on the preceding phase of alpha oscillations (~7-12 Hz). In audition, however, such an effect seemed to be absent. Due to the transient nature of its input, the auditory system might be particularly vulnerable to information loss that occurs if relevant information coincides with the low excitability phase of the oscillation. We therefore hypothesised that effects of oscillatory phase in audition will be restored if auditory events are made task-irrelevant and information loss can be tolerated. To this end, we collected electroencephalography (EEG) data from 29 human participants (21F) while they detected pure tones at one sound frequency and ignored others. Confirming our hypothesis, we found that the neural response to task-irrelevant but not to task-relevant tones depends on the pre-stimulus phase of neural oscillations. Alpha oscillations modulated early stages of stimulus processing, whereas theta oscillations (~3-7 Hz) affected later components, possibly related to distractor inhibition. We also found evidence that alpha oscillations alternate between sound frequencies during divided attention. Together, our results suggest that the efficacy of auditory oscillations depends on the context they operate in, and demonstrate how they can be employed in a system that heavily relies on information unfolding over time.Significance StatementThe phase of neural oscillations shapes visual processing, but such an effect seemed absent in the auditory system when confronted with temporally unpredictable events. We here provide evidence that oscillatory mechanisms in audition critically depend on the degree of possible information loss during the oscillation’s low excitability phase, possibly reflecting a mechanism to cope with the rapid sensory dynamics that audition is normally exposed to. We reach this conclusion by demonstrating that the processing of task-irrelevant but not task-relevant tones depends on the pre-stimulus phase of neural oscillations during selective attention. During divided attention, cycles of alpha oscillations seemed to alternate between possible acoustic targets similar to what was observed in vision, suggesting an attentional process that generalises across modalities.
Citizens' acceptance of prefabricated housing in China: the role of procedural justice and uncertainty
Authors: Zhou Zhenzong , Wei Chen , Shen Geoffrey Qiping , Xue Jin , Liu Yongyue , Wang Yaowu , Man Qingpeng 
Published: August 2024

PurposeThis study explores citizens’ acceptance of prefabricated housing (PH) from the perspective of socio-demographic and psychological factors, aiming to reveal the formation of PH acceptance and realize a sustainable development of PH.Design/methodology/approachThis study proposed hypotheses drawing on procedural justice theory and uncertainty management theory. A survey of 245 respondents was conducted, and the collected data was analyzed in a stepwise multiple regression model. Then, the psychological influencing mechanism was demonstrated using a mediation model.FindingsResults of the data analysis manifested that citizens’ acceptance of PH was influenced by socio-demographic and psychological factors, where psychological factors had more significant effects on acceptance than socio-demographic factors. The psychological mechanism was examined by verifying the mediating role of uncertainty between procedural justice and the acceptance of PH. Furthermore, a scientific strategy for developing PH was proposed based on this empirical study.Originality/valueThis study extends the knowledge of procedural justice theory by investigating people’s acceptance in the PH context. This study is also one of the first studies to unveil the psychological mechanism toward a high-cost product with invisible technological innovation. This study contributes to the literature by introducing uncertainty management theory to a controversial issue, examining and expanding its application in a complicated context. Moreover, results highlight the positive influence of fair processes on controversial issues.