bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus 1 CNS infection
Authors: Ding Xiangning , Lai Xin , Klæstrup Ida Hyllen , Jensen Sara R. N. , Nielsen Morten M , Thorsen Kasper , Romero-Ramos Marina , Luo Yonglun , Lin Lin , Reinert Line S , Paludan Søren R 
Published: August 2024

AbstractHerpes Simplex Virus 1 (HSV-1) is a common human neurotropic virus with the majority of adults harboring latent-recurrent infections. In rare cases, HSV-1 infection can access the central nervous system through the neuronal route and develop into life-threatening encephalitis. Here, we used a mouse model for HSV-1 infection to describe the transcriptomic profile of the infected brain stem at the single-cell level and with temporal resolution. Among resident brain cells, microglia increased in proportion during the course of infection, while astrocytes, pericytes, and endothelial cell levels decrease. At the levels of peripheral immune cells, we found notably monocytes to strongly influx the infected brain. Large dynamic changes were found in the abundance of subpopulations of the different cell types following virus infection. For instance, we identify one subpopulation of microglia exhibiting very high type I interferon and chemokine expression early during infection. This population was also enriched for viral transcripts, suggesting localization at foci of infection, and orchestrating recruitment of other immune cells. In contrast, for the infiltrating monocytes, we identified a larger panel of unique subpopulations with antiviral and inflammatory phenotypes, and found not all of these being highly positive for viral transcripts, thus indicating monocyte activities beyond the infected brain areas. Finally, investigation of endothelial cell cross-talk with other cell types revealed that cytokines derived from microglia and monocyte, but also T cells, contribute to disturbance of the blood brain barrier. Our work thus reveals for the first time the complex nature of the cellular response in the virus-infected brain, which seeks to eliminate infection but can also prime for pathological changes.
Using lineage-specific patterns to understand convergence of enzymatic functions led to the identification of Moraceae-specific P450s involved in furanocoumarin biosynthesis
Authors: Bouillé Alexandre , Kumari Rashmi , Olry Alexandre , Charles Clément , Nelson David R , Larbat Romain , Thornton Janet , Villard Cloé , Hehn Alain 
Published: August 2024

SummarySpecialized metabolites are molecules involved in plants interaction with their environment. Elucidating their biosynthetic pathways is a challenging but rewarding task, leading to societal applications and ecological insights. Furanocoumarins emerged multiple times in Angiosperms, raising the question of how different enzymes evolved into catalyzing identical reactions.To identify enzymes producing lineage-specific metabolites, an evolutionary-based approach was developed and applied to furanocoumarin biosynthesis inFicus carica(Moraceae). This led to the characterization of CYP71B129-131a, three P450 enzymes whose evolution of the function was investigated using phylogenetics, structural comparisons and site-directed mutagenesis.CYP71B129 and CYP71B130,131a were found to hydroxylate umbelliferone (coumarin) and xanthotoxin (furanocoumarin), respectively. Results suggest that CYP71Bs xanthotoxin hydroxylase activity results from duplications and functional divergence of umbelliferone hydroxylase genes. Structural comparisons highlighted an amino acid affecting CYP71Bs substrate specificity, which may play a key role in allowing xanthotoxin hydroxylation in several P450 subfamilies.CYP71B130-131a characterization validates the proposed enzyme-discovery approach, which can be applied to different pathways and help to avoid the classic bottlenecks of specialized metabolism elucidation. The CYP71Bs also exemplify how furanocoumarin-biosynthetic enzymes can stem from coumarin-biosynthetic ones and provides insights into the molecular mechanisms underlying the multiple emergences of xanthotoxin hydroxylation in distant P450 subfamilies.
Tim-3 promotes viral infection by suppressing USP25-TRAF3-IRF7 signaling pathway
Authors: Du Lin , Chen Jinjie , Du Chunxiao , Chen Junrui , Wang Chaoxiang , Bao Bing , Lv Zhonglin , Xing Chen , Liang Meng , Wang Lanying , Xie Shun , Li Yuxiang , Wang Zhiding , Li Ge , Zhang Jun , Han Gencheng 
Published: August 2024

AbstractTim-3, an immune checkpoint inhibitor, plays key roles in maintaining immune homeostasis and is involved in viral evasion. However, the precise role of Tim-3 in viral infection remains to be determined. USP25 is one of the deubiquitinating enzymes that serves to initiate antiviral immunity by deubiquitinating TRAF3 and triggering the anti-viral signaling pathway. Here we found that Tim-3 specific knockout in myeloid cells leads to enhanced anti-viral immunity in mice with VSV encephalitis by increasing type I interferon response. Mechanistically, Tim-3 inhibits the expression of USP25 via STAT1, interacts with USP25 but does not regulate its post-translational modification, and as a result, Tim-3 inhibits USP25 mediated deubiquitination of TRAF3, promotes k48-linked ubiquitination and degradation of TRAF3, and then inhibits the phosphorylation of IRF7, finally down-regulates the interferon response. These findings provide new insights into the function of Tim-3 in antiviral immunity and its related clinical significance.
An extraordinary larval-like teleost fish from the Eocene of Bolca
Authors: Davesne Donald , Carnevale Giorgio 
Published: August 2024

ABSTRACT“Pegasus”volansis a highly unusual fossil teleost fish from the celebrated Eocene Bolca Lagerstatte. The fossil, known on the basis of two specimens, has been historically assigned to seamoths (Pegasidae), then to oarfish and relatives (Lampriformes). We describe its enigmatic skeletal anatomy in detail, and provide a new genus name. “Pegasus”volansis an extremely elongate and slender animal, with long anal and dorsal fins and a very well-developed first dorsal-fin ray reminiscent to the vexillum of some modern teleost larvae. Most striking is its extreme ventral projection of the pelvic girdle (basipterygium), associated with an element of the pectoral girdle (a long process of the coracoid) and developed pelvic-fin rays. The strongly reduced abdominal region suggests that “Pegasus”volanshad an external gut, once again reminiscent of those of certain larval teleosts. The unique character state combination displayed by “Pegasus”volansmake it impossible to assign it to a specific subclade within perch-like spiny-rayed fishes (Percomorpha). Nevertheless, it offers a valuable perspective on the diversity of morphologies and ecological niches occupied by teleost fishes of the early Eocene Bolca fauna.
Compressed higher-order structures facilitate human knowledge network learning
Authors: Ren Xiangjuan , Wang Muzhi , Qin Tingting , Fang Fang , Li Aming , Luo Huan 
Published: August 2024

AbstractKnowledge seeking is innate to human nature, yet integrating vast and fragmented information into a unified network is a daunting challenge, especially in the information explosion era. Graph theory describes knowledge as a network characterising relationships (edges) between isolated data (nodes). Accordingly, knowledge learning could be abstracted as network navigation through random walks, where local connections are gradually learned and integrated to form the global picture. To facilitate network learning, we develop a novel “compressive learning” approach that decomposes network structures into substructures based on higher-order inhomogeneity properties and designs pre-learning paths highlighting key substructures. Large-scale behavioural experiments and magnetoencephalography (MEG) recordings demonstrate its effectiveness and better network formation in human brains. Hypergraph-based computational models reveal that the pre-learning path helps establish the core network skeleton to efficiently accommodate late inputs. Overall, higher-order network structures are crucial to network learning and can be utilised to better “connect the dots”.
Confidence over competence: Real-time integration of social information in human continuous perceptual decision-making
Authors: Schneider Felix , Calapai Antonino , Mundry Roger , Báez-Mendoza Raymundo , Gail Alexander , Kagan Igor , Treue Stefan 
Published: August 2024

AbstractHuman perception is susceptible to social influences. To determine if and how individuals opportunistically integrate real-time social information about noisy stimuli into their judgment, we tracked perceptual accuracy and confidence in social (dyadic) and non-social (solo) settings using a novel continuous perceptual report (CPR) task with peri-decision wagering. In the dyadic setting, most participants showed a higher degree of perceptual confidence. In contrast, average accuracy did not improve compared to solo performance. Underlying these net effects, partners in the dyad exhibit mutual convergence of accuracy and confidence, benefitting less competent or confident individuals, at the expense of the better performing partner. In conclusion, real-time social information asymmetrically shapes human perceptual decision-making, with dyads expressing more confidence without a matching gain in overall competence.
The multi-stage plasticity in the aggression circuit underlying the winner effect
Authors: Yan Rongzhen , Wei Dongyu , Varshneya Avni , Shan Lynn , Asencio Hector J. , Lin Dayu 
Published: August 2024

SummaryWinning increases the readiness to attack and the probability of winning, a widespread phenomenon known as the “winner effect”. Here, we reveal a transition from target-specific to generalized aggression enhancement over 10 days of winning in male mice, which is supported by three stages of plasticity in the ventrolateral part of the ventromedial hypothalamus (VMHvl), a critical node for aggression. Over 10-day winning, VMHvl cells experience monotonic potentiation of long-range excitatory inputs, a transient local connectivity strengthening, and a delayed excitability increase. These plasticity events are causally linked. Optogenetically coactivating the posterior amygdala (PA) terminals and VMHvl cells potentiates the PA-VMHvl pathway and triggers the cascade of plasticity events as those during repeated winning. Optogenetically blocking PA-VMHvl synaptic potentiation eliminates all winning-induced plasticity. These results reveal the complex Hebbian synaptic and excitability plasticity in the aggression circuit during winning that ultimately leads to an increase in “aggressiveness” in repeated winners.
Ex situspawning, larval development, and settlement in the massive reef-building coralPorites lobatain Palau
Authors: Bennett Matthew-James , Grupstra Carsten G.B. , Da-Anoy Jeric , Andres Maikani , Holstein Daniel , Rossin Ashley , Davies Sarah W. , Meyer-Kaiser Kirstin S. 
Published: August 2024

AbstractReproduction, embryological development, and settlement of corals are critical for survival of coral reefs through larval propagation. Yet, for many species of corals, a basic understanding of the early life-history stages is lacking. In this study, we report our observations forex situreproduction in the massive reef-building coralPorites lobataacross two years. Spawning occurred in April and May, on the first day after the full moon with at least two hours of darkness between sunset and moonrise, on a rising tide. Only a small proportion of corals observed had mature gametes or spawned (17 – 35%). Eggs were 185 – 311 μm in diameter, spherical, homogenous, and provisioned with 95 – 155 Symbiodiniaceae algae. Males spawned before females, andex situfertilization rates were high for the first 2 hours after egg release.P. lobatalarvae were elliptical, approximately 300 μm long, and symbiotic. Just two days after fertilization, many larvae swam near the bottom of culture dishes and were competent to settle. Settlers began calcification two days after metamorphosis, and tentacles were developed 10 days after attachment. Our observations contrast with previous studies by suggesting an abbreviated pelagic larval period inP. lobata, which could lead to the isolation of some populations. The high thermal tolerance and a broad geographic range ofP. lobatasuggest this species could locally adapt to a wide range of environmental conditions, especially if larvae are locally retained. The results of this study can inform future work on reproduction, larval biology, dispersal, and recruitment ofP. lobata, which could have an ecological advantage over less resilient coral species under future climate change.
What did the dove sing to Pope Gregory? Ancestral melody reconstruction in Gregorian chant using Bayesian phylogenetics
Authors: Ballen Gustavo A. , Mühlová Klára Hedvika , Hajič Jan 
Published: August 2024

AbstractAn attractive goal in the study of Gregorian chant melodies is reconstructing unobserved melodies as they may have been transmitted along the history of chant, especially as early chant notation does not capture pitch exactly. We propose doing this computationally using Ancestral State Reconstruction (ASR) over phylogenetic trees. Bayesian phylogenetic trees have shown promise as a tool to study the evolution of chant melodies, by inferring a plausible topology of chant transmission. However, the inferred trees cannot be used as ASR inputs directly, because they are undirected, and their branch lengths conflate time and evolutionary rate. We therefore first apply Divergence Time Estimation (DTE) to separate them and represent the tree in a directed form on the time dimension. Using ASR, we then obtain reconstructions of melodies for each of the ancestral nodes, in addition to their distribution in time obtained from DTE, and thus we obtain a phylogeny of chant melody with a music-historical interpretation. We applied this method to the Christmas Vespers dataset, and compare the results against musicological knowledge and melodies reconstructed at Solesmes using methods of contemporary philology, which shows potential for reconstructing cultural transmission through time.
Differential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates
Authors: Erkamp Nadia A. , Farag Mina , Qiu Yuanxin , Qian Daoyuan , Sneideris Tomas , Wu Tingting , Welsh Timothy J. , Ausserwӧger Hannes , Krug Tommy J. , Weitz David A. , Lew Matthew , Knowles Tuomas P. J. , Pappu Rohit V. 
Published: August 2024

AbstractBiomolecular condensates form via macromolecular phase separation, giving rise to coexisting phases delineated by interfaces. Here, we characterize the structures of interfaces formed by phase separation driven by heterotypic interactions in ternary mixtures of two types of RNA molecules and polyethylene glycol. We find that purine-rich RNAs are scaffolds that drive phase separation via strong heterotypic interactions. Conversely, pyrimidine-rich RNA molecules are defined by weaker heterotypic interactions. They function as adsorbents that accumulate at and wet the interfaces of coexisting phases formed by phase separation of scaffolds. Our computations predict that scaffolds and adsorbents have different non-random orientational preferences at interfaces. We tested these predictions using single-molecule super resolution imaging that tracks the motions of fluorogenic probes that are bound to RNA molecules. Motions parallel to the interface were found to be faster than motions perpendicular to the interface. These findings support previous predictions regarding anisotropies of motions at interfaces.
MAASTY: A (dis)ordered copolymer for structural determination of human membrane proteins in native nanodiscs
Authors: Pugh Ciara Frances , Præstegaard Kaia Fiil , Feilen Lukas Peter , Živković Dušan , Borthwick Neil Jean , de Lichtenberg Casper , Bolla Jani R. , Autzen Anton Allen Abbotsford , Autzen Henriette Elisabeth 
Published: August 2024

AbstractAmphiphilic copolymers capable of extracting membrane proteins directly from lipid bilayers into ”native nanodiscs” offer a simplified approach for preparing membrane proteins in lipid nanodiscs compared to approaches that rely on detergent. Amphiphilicity, length, and composition influence the performance of copolymers, in addition to the protein itself and the purification conditions used. Here, we report a copolymer composed of methacrylic acid and styrene, which we term MAASTY, leveraging the inherent monomer reactivity ratios to create an anionic copolymer with a statistical distribution of monomers. We show that MAASTY can be used for high-resolution structural determination of a human membrane protein with single particle cryo-electron microscopy, preserving endogenous lipids. Moreover, MAASTY copolymers effectively solubilize a broad range of lipid species and a wide range of different, eukaryotic membrane proteins from mammalian cells. We find that MAASTY copolymers are promising as effective solubilizers of membrane proteins and offer a new chemical platform for structural and functional characterization of membrane proteins in native nanodiscs.
Clusters of deep intronic RbFox motifs regulate mammalian alternative splicing
Authors: Tomassoni-Ardori Francesco , Palko Mary Ellen , Galloux Melissa , Tessarollo Lino 
Published: August 2024

AbstractThe RbFox RNA binding proteins regulate alternative splicing of genes governing mammalian development and organ function. They bind to the RNA sequence GCAUG with high affinity but also non-canonical secondary motifs in a concentration dependent manner. However, the hierarchical requirement of RbFox motifs, which are widespread in the genome, is still unclear. Here we show that deep intronic, tightly clustered RbFox1 motifs cooperate and are necessary in regulating splicing of alternative exons. By employing recombineering mutagenesis in bacterial artificial chromosomes we found that tightly clustered (U)GCAUG motifs in the middle of 50 Kb introns are necessary for RbFox regulation of gene isoforms expression. Bioinformatic analysis revealed that (U)GCAUG-clusters are widely present in both mouse and human genes and are embedded in sequences binding the large assembly of splicing regulators. Integrative data analysis from eCLIP and RNAseq experiments showed a global increase in RNA isoform modulation of genes with Rbfox1 eCLIP-peaks associated with these clusters. These data suggest that clustered distal intronic Rbfox-binding motifs are important determinants of RbFox1 function in the mammalian genome and provide a target for identification of pathogenic mutations.
The ZIP8 A391T Crohn’s disease-linked risk variant induces colonic metal ion dyshomeostasis, microbiome compositional shifts, and inflammation
Authors: Yang Julianne C. , Zhao Matthew , Chernikova Diana , Arias-Jayo Nerea , Zhou Yi , Situ Jamilla , Gutta Arjun , Chang Candace , Liang Fengting , Lagishetty Venu , Jacobs Jonathan P. 
Published: August 2024

ABSTRACTThe pathogenesis of Crohn’s disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohn’s disease-associated variant rs13107325 in the SLC39A8 gene results in an A391T substitution in the ZIP8 metal ion transporter and has previously been linked to alterations in the colonic microbiome in variant carriers. We hypothesized that the A391T substitution alters metal ion homeostasis in the colonic mucosal-luminal interface, thereby inducing dysbiosis which may promote intestinal inflammation. To evaluate this hypothesis, we generated a SLC39A8 A393T mouse model (matching human A391T). Consistent with an effect of the variant on ZIP8 function, homozygous A393T mice exhibited increased cobalt in the colonic mucosa, but reduced iron, zinc, manganese, cobalt, copper, and cadmium in the colonic lumen. We performed 16S rRNA gene sequencing of colon samples and histological scoring of colon tissue collected from the SLC39A8 A393T mouse model at different ages. We identified variant-linked effects on microbiome beta diversity in 2-month, 3-4 month, and 12-month old mice and spontaneous intestinal inflammation in 10-month but not 5-month old mice. Predicted pathway analysis of the microbiome samples revealed differential enrichment of iron-, zinc- and cobalt-dependent pathways in A393T mice compared to wild-type controls. These results suggest that the variant in SLC39A8 primarily restricts metal availability to the microbiota, resulting in compositions that can adapt to the environment, and that A393T-linked dysbiosis occurs prior to the onset of inflammation. This study paves the way for future studies investigating risk variants as microbiome-disease modifiers.NEW & NOTEWORTHYMice recapitulating the human A391T Crohn’s disease-linked risk variant in the SLC39A8-encoded ZIP8 transporter exhibit reduced luminal trace metals and an altered microbiome composition. The microbiome compositional shift occurs prior to the onset of spontaneous colonic inflammation. This study supports an emerging paradigm by which genetic risk for inflammatory bowel disease may confer disease susceptibility through modulation of the gut microbiome.
Technical Assessment on Proteonano™: A Robust Platform for Deep Plasma Proteomics Study
Authors: Wang Yi , Zhang Yonghao , Ouyang Xiehua , Wu Hao 
Published: August 2024

ABSTRACTComplete profiling of human plasma proteome is an immerse source for disease biomarker discovery. Cutting-edge mass spectrometers, like ThermoFisher’s Orbitrap Astral, have promised unprecedented insights into the exploration of multiple protein biomarkers from human plasma samples. However, large-scale, deep profiling of the human plasma proteome, especially low-abundant proteins (LAPs, <10 ng mL−1), in a robust and fast way remains challenging. This is largely due to the lack of standardized and automated workflows including LAPs enrichment, reduction, and enzymatic digestion procedures. Until now, these complex procedures have not been incorporated into a streamlined workflow to achieve reproducibility, high-throughput, and deep proteome coverage.Here we report the Proteonano™ Ultraplex Proteomics Platform for large cohort plasma proteomics studies with robustness and high throughput by standardizing workflow by incorporating the Proteonano™ platform and high-resolution mass spectrometers, including Orbitrap Exploris™ 480, Orbitrap Astral™, and timsTOF Pro 2. This pipeline demonstrates excellent stability and reproducibility, with tunable balance between detection depth and throughput. We further demonstrate the utility of this platform for biomarker discovery in an Alzheimer disease related cohort. This harmonized platform enables robust, fast and large-cohort plasma proteomics studies to meet the need to discovering new biomarkers.