bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-wide activity-identity mapping of neural networks associated with prosocial motivation in rats
Authors: Ruzal Keren , Trachtenberg Estherina , Kantor Ben , Flumin Hila , Roemer Adin , Crespo Andres , Kohl Johannes , Bartal Inbal Ben-Ami 
Published: December 2023

SummaryA prosocial response to others in distress is an important driver of behavior across social species. To investigate the neurobiological mechanism leading to prosocial behavior, we use a helping behavior test wherein rats may release a trapped conspecific by opening a restrainer door. To ensure rats were not acting for social interaction, a separation divider prevented post-release contact (“separated” test). Despite the divider, most rats consistently opened the restrainer, demonstrating prosocial motivation. Brain-wide c-Fos analysis conducted via our opensource software "Brainways", revealed activity in empathy-related regions, including the anterior cingulate and insular cortices. Nucleus accumbens activity, previously recorded during helping, was not significant in the“separated” test. Chemogenetic manipulations of the accumbens did not prevent helping, suggesting that its activity reflects contact seeking. Mapping of oxytocin and dopamine receptors on active cells revealed region-specific recruitment of these subpopulations, depending on the social context. Network connectivity analysis highlights context-dependent functional subcircuits.
Nuclear cytoophidia assembly represses transcriptional activity to control skeletal development and homeostasis
Authors: Xu Cheng , Wei Zhixin , Lv Longfei , Dong Xiaoyu , Xia Wenwen , Xing Junqiao , Liu Hongni , Zhao Xue , Liu Yuan , Wang Weihua , Jiang Haochen , Gong Yeli , Liu Cong , Xu Kai , Wang Siyuan , Akimoto Yoshie , Hu Zhangfeng 
Published: December 2023

ABSTRACTCompartmentation via filamentation is an evolutionarily conserved subcellular structure that fine-tunes the inherent activity of proteins. Cytoophidia represent a typical class of filamentous structures controlling enzymatic activities. Despite eukaryotic cells containing both cytoplasmic cytoophidia and nuclear cytoophidia, the physiological significance of nuclear cytoophidia is largely unknown. Here we show that nuclear filamentation inhibits the transcriptional activity of Impdh2 required for limb formation and bone resorption. Impdh2 deletion in mouse limb mesenchymal progenitors causes severe skeletal dysplasia by impairing endochondral ossification and chondrocyte differentiation. Additionally, Impdh2 deficiency in myeloid lineages leads to an increased bone mass via impeding osteoclast differentiation. Furthermore, Impdh2 regulates osteoclastic mitochondrial biogenesis and function. We propose that the nuclear compartmentalization of Impdh2 regulates the transcriptional activity during skeletal development and homeostasis.
Profiling age and body fluid DNA methylation markers using nanopore adaptive sampling
Authors: Yuen Zaka Wing-Sze , Shanmuganandam Somasundhari , Stanley Maurice , Jiang Simon , Hein Nadine , Daniel Runa , McNevin Dennis , Jack Cameron , Eyras Eduardo 
Published: December 2023

AbstractDNA methylation plays essential roles in regulating physiological processes, from tissue and organ development to gene expression and aging processes and has emerged as a widely used biomarker for the identification of body fluids and age prediction. Currently, methylation markers are targeted independently at specific CpG sites, as part of a multiplexed assay, rather than through a unified assay. Methylation detection is also dependent on divergent methodologies, ranging from enzyme digestion and affinity enrichment to bisulfite treatment, alongside various technologies for high-throughput profiling, including microarray and sequencing. In this pilot study, we test the simultaneous identification of age-associated and body fluid-specific methylation markers using a single technology, nanopore adaptive sampling. This innovative approach enables the profiling of multiple CpG marker sites across entire gene regions from a single sample without the need for specialized DNA preparation or additional biochemical treatments. Our study demonstrates that adaptive sampling achieves sufficient coverage in regions of interest to accurately determine the methylation status, shows a robust consistency with whole-genome bisulfite sequencing data, and corroborates known CpG markers of age and body fluids. Our work also resulted in the identification of new sites strongly correlated with age, suggesting new possible age methylation markers. This study lays the groundwork for the systematic development of nanopore-based methodologies in both age prediction and body fluid identification, highlighting the feasibility and potential of nanopore adaptive sampling while acknowledging the need for further validation and expansion in future research.
Subthalamic nucleus neurons encode syllable sequence and phonetic characteristics during speech
Authors: Lipski W.J. , Bush A. , Chrabaszcz A. , Crammond D.J. , Fiez J.A. , Turner R.S. , Richardson R.M. 
Published: December 2023

AbstractSpeech is a complex behavior that can be used to study unique contributions of the basal ganglia to motor control in the human brain. Computational models suggest that the basal ganglia encodes either the phonetic content or the sequence of speech elements. To explore this question, we investigated the relationship between phoneme and sequence features of a spoken syllable triplet and the firing rate of subthalamic nucleus (STN) neurons recorded during the implantation of deep brain stimulation (DBS) electrodes in individuals with Parkinson’s disease. Patients repeated aloud a random sequence of three consonant-vowel (CV) syllables in response to audio cues. Single-unit extracellular potentials were sampled from the sensorimotor STN; a total of 227 unit recordings were obtained from the left STN of 25 subjects (4 female). Of these, 113 (50%) units showed significant task-related increased firing and 53 (23%) showed decreased firing (t-test relative to inter-trial period baseline, p<0.05). Linear regression analysis revealed that both populations of STN neurons encode phoneme and sequence features of produced speech. Maximal phoneme encoding occurred at the time of phoneme production, suggesting efference copyor sensory-related processing, rather than speech motor planning (-50ms and +175ms relative to CV transition for consonant and vowel encoding, respectively). These findings demonstrate that involvement of the basal ganglia in speaking includes separate single unit representations of speech sequencing and phoneme selection in the STN.
Broad H3K4me3 Domain Is Associated with Spatial Coherence during Mammalian Embryonic Development
Authors: Cao Xuan , Ma Terry , Fan Rong , Yuan Guo-Cheng 
Published: December 2023

SummaryIt is well known that the chromatin states play a major role in cell-fate decision and cell-identity maintenance; however, the spatial variation of chromatin statesin situremains poorly characterized. Here, by leveraging recently available spatial-CUT&Tag data, we systematically characterized the global spatial organization of the H3K4me3 profiles in a mouse embryo. Our analysis identified a subset of genes with spatially coherent H3K4me3 patterns, which together delineate the tissue boundaries. The spatially coherent genes are strongly enriched with tissue-specific transcriptional regulators. Remarkably, their corresponding genomic loci are marked by broad H3K4me3 domains, which is distinct from the typical H3K4me3 signature. Spatial transition across tissue boundaries is associated with continuous shortening of the broad H3K4me3 domains as well as expansion of H3K27me3 domains. Our analysis reveals a strong connection between the genomic and spatial variation of chromatin states, which may play an important role in embryonic development.
Structural mechanism of angiogenin activation by the ribosome
Authors: Loveland Anna B. , Koh Cha San , Ganesan Robin , Jacobson Allan , Korostelev Andrei A. 
Published: December 2023

AbstractAngiogenin, an RNase A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases, and epigenetic inheritance. Upon activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, producing nicked tRNA (also known as tRNA halves, tiRNAs or tsRNAs) and resulting in translation repression. The catalytic activity of isolated angiogenin, however, is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle. Here, we uncover these mechanisms using biochemical assays and cryogenic electron microscopy. Our work reveals that the cytosolic ribosome is the long-sought activator of angiogenin. A 2.8-Å resolution cryo-EM structure features angiogenin bound in the A site of the 80S ribosome. The C-terminal tail of angiogenin is rearranged by interactions with the ribosome to activate the RNase catalytic center, making the enzyme several orders of magnitude more efficient in tRNA cleavage. Additional 80S•angiogenin structures capture how the tRNA substrate is directed by the ribosome next to angiogenin’s active site, demonstrating that the ribosome acts as the specificity factor. Our findings therefore suggest that angiogenin is activated by ribosomes with a vacant A site, whose abundance increases during cellular stresses.
Unveiling interactions of spatial-temporal information in tactile motion perception
Authors: Qu Boyi , Tan Xiaojun , Tang Zheng , Friedman Robert M. , Wang Haiming , Lan Lan , Schriver Kenneth E , Pan Gang , Lai Hsin-Yi 
Published: December 2023

AbstractThe intricate interplay of spatial and temporal information in tactile-motion perception remains elusive. Despite strides in decoding neural signals for direction, speed and texture in tactile perception, nuanced interactions persist as challenges. Addressing this, we investigated direction and speed tactile perception, exploring the intricate spatial-temporal dynamics. Psychophysical experiments manipulated direction and speed parameters using a laboratory-designed fingerpad ball-stimulator. A pivotal discovery includes quadrant-dependent anisotropic distortion in perceived motion direction, expanding the well-known notion of a specific preferred orientation. Spatial features primarily influence inherent responses, while temporal features impact stimulus-specific responses, shedding light on dynamic directional perception. The introduction of a psychometric function improved the modeling of tactile-motion speed perception, incorporating both linear and nonlinear components for a more accurate representation. This study provides intriguing insights into the neural mechanisms in tactile-motion perception, with potential applications for somatosensation in brain-machine interfaces.TeaserThis study unveils the intricate interplay of perceiving tactile motion, shedding light on the mysteries of tactile sensations.
Live microscopy of multicellular spheroids with the multi-modal near-infrared nanoparticles reveals differences in oxygenation gradients
Authors: Debruyne Angela C. , Okkelman Irina A. , Heymans Nina , Pinheiro Cláudio , Hendrix An , Nobis Max , Borisov Sergey M. , Dmitriev Ruslan I. 
Published: December 2023

AbstractAssessment of hypoxia, nutrients, metabolite gradients, and other hallmarks of the tumor microenvironment within 3D multicellular spheroid and organoid models represents a challenging analytical task. Here, we report red/near-infrared emitting cell staining O2-sensitive nanoparticles, which enable measurements of spheroid oxygenation on a conventional fluorescence microscope. Nanosensor probes, termed ’MMIR’ (multi-modal infrared), incorporate a near-infrared O2-sensitive metalloporphyrin (PtTPTBPF) and a deep red aza-BODIPY reference dyes within a biocompatible polymer shell, allowing oxygen gradients quantificationviafluorescence ratio and phosphorescence lifetime readouts. We optimized staining techniques and evaluated nanosensor probe characteristics and cytotoxicity. Subsequently, we applied nanosensors to the live spheroid models based on HCT116, DPSCs, and SKOV3 cells, at rest and treated with drugs affecting cell respiration. We found that the growth medium viscosity, spheroids size, and formation method influenced spheroid oxygenation.Unexpectedly, some spheroids (produced from HCT116 and dental pulp stem cells) exhibited ’inverted’ oxygenation gradients, with higher core oxygen levels than the periphery. This contrasted with the frequently encountered ‘normal’ gradient of hypoxia towards the core caused by diffusion. Further microscopy analysis of spheroids with an “inverted” gradient demonstrated metabolic stratification of cells within spheroids: thus, autofluorescence FLIM of NAD(P)H revealed the formation of glycolytic core, and localization of OxPhos-active cells at the periphery. Collectively, we demonstrate a strong potential of NIR-emitting ratiometric nanosensors for advanced microscopy studies targeting live and quantitative real-time monitoring of cell metabolism and hypoxia in complex 3D tissue models.Graphical abstract
Subcallosal area 25: its responsivity to the stress hormone cortisol and its opposing effects on appetitive motivation in marmosets
Authors: Banai Tizkar Rana , McIver Lauren , Wood Christian Michael , Roberts Angela Charlotte 
Published: December 2023

AbstractAberrant activity in caudal subcallosal anterior cingulate cortex (scACC) is implicated in depression and anxiety symptomatology, with its normalisation a putative biomarker of successful treatment response. The function of scACC in emotion processing and mental health is not fully understood despite its known influence on stress-mediated processes through its rich expression of mineralocorticoid and glucocorticoid receptors. Here we examine the causal interaction between area 25 within scACC (scACC-25) and the stress hormone, cortisol, in the context of anhedonia and anxiety-like behaviour. Moreover, the overall role of scACC-25 in hedonic capacity and motivation is investigated under transient pharmacological inactivation and overactivation. The results suggest that a local increase of cortisol in scACC-25 shows a rapid induction of anticipatory anhedonia and increased responsiveness to uncertain threat. Separate inactivation and overactivation of scACC-25 increased and decreased motivation and hedonic capacity, respectively, likely through different underlying mechanisms. Together, these data show that area scACC-25 has a causal role in consummatory and motivational behaviour and produces rapid responses to the stress hormone cortisol, that mediates anhedonia and anxiety-like behaviour.
Learning of object-in-context sequences in freely-moving macaques
Authors: Abbaspoor S. , Rahman K. , Zinke W. , Hoffman K.L. 
Published: December 2023

ABSTRACTFlexible learning is a hallmark of primate cognition, which arises through interactions with changing environments. Studies of the neural basis for this flexibility are typically limited by laboratory settings that use minimal environmental cues and restrict interactions with the environment, including active sensing and exploration. To address this, we constructed a 3-D enclosure containing touchscreens on its walls, for studying cognition in freely moving macaques. To test flexible learning, two monkeys completed trials consisting of a regular sequence of object selections across four touchscreens. On each screen, the monkeys had to select by touching the sole correct object item (‘target’) among a set of four items, irrespective of their positions on the screen. Each item was the target on exactly one screen of the sequence, making correct performance conditioned on the spatiotemporal sequence rule across screens. Both monkeys successfully learned multiple 4-item sets (N=14 and 22 sets), totaling over 50 and 80 unique, conditional item-context memoranda, with no indication of capacity limits. The enclosure allowed freedom of movements leading up to and following the touchscreen interactions. To determine whether movement economy changed with learning, we reconstructed 3D position and movement dynamics using markerless tracking software and gyroscopic inertial measurements. Whereas general body positions remained consistent across repeated sequences, fine head movements varied as monkeys learned, within and across sequence sets, demonstrating learning set or “learning to learn”. These results demonstrate monkeys’ rapid, capacious, and flexible learning within an integrated, multisensory 3-D space. Furthermore, this approach enables the measurement of continuous behavior while ensuring precise experimental control and behavioral repetition of sequences over time. Overall, this approach harmonizes the design features that are needed for electrophysiological studies with tasks that showcase fully situated, flexible cognition.
Sex-specific behavioral features of juvenile and adult haploinsufficientScn2a+/−female mice, model of Autism Spectrum Disorder
Authors: Marcantonio Wendy , Simonti Martina , Léna Isabelle , Mantegazza Massimo 
Published: December 2023

AbstractVariants of theSCN2Agene, encoding the NaV1.2 sodium channel, cause a spectrum of neurodevelopmental and epileptic disorders, and are among those that show the strongest association with Autism Spectrum Disorder (ASD). ASD has a male-bias prevalence, but several studies have proposed that female prevalence may be underestimated due to different symptomatic expression compared with males. However, it is unclear whether this is related to actual different pathological features or to greater masking abilities in females.Studies onScn2a+/−mice, a model ofSCN2Ahaploinsufficiency and ASD, have shown an age-dependent ASD-like phenotype attenuated at adulthood in males. However, little is known about the behavioral features ofScn2a+/−female mice. We performed a battery of behavioral tests that are relevant for assessing ASD-like features, investigating juvenile and adultScn2a+/−female mice.Our results demonstrate that femaleScn2a+/−mice exhibit an overall milder phenotype than males, showing increased sociability and increased risk taking in juveniles, hyper-reactivity to cold stimuli in adults, altered decision-making related behaviors in both. Thus, this is consistent with the male-bias prevalence of ASD and the existence of different ASD phenotypic features in males and females. Both genders should be investigated in studies of mouse models of ASD.
Evolution of extended-spectrum β-lactamase-producing ST131Escherichia coliat a single hospital over 15 years
Authors: Cho Shu-Ting , Mills Emma G. , Griffith Marissa P. , Nordstrom Hayley R. , McElheny Christi L. , Harrison Lee H. , Doi Yohei , Van Tyne Daria 
Published: December 2023

AbstractEscherichia colibelonging to sequence type ST131 constitute a globally distributed pandemic lineage that causes multidrug-resistant extra-intestinal infections. ST131E. colifrequently produce extended-spectrum β-lactamases (ESBLs), which confer resistance to many β-lactam antibiotics and make infections difficult to treat. We sequenced the genomes of 154 ESBL-producingE. coliclinical isolates belonging to the ST131 lineage from patients at the University of Pittsburgh Medical Center (UPMC) between 2004 and 2018. Isolates belonged to the well described ST131 clades A (8%), B (3%), C1 (33%), and C2 (54%). An additional four isolates belonged to another distinct subclade within clade C and encoded genomic characteristics that have not been previously described. Time-dated phylogenetic analysis estimated that the most recent common ancestor (MRCA) for all clade C isolates from UPMC emerged around 1989, consistent with previous studies. We identified multiple genes potentially under selection in clade C, including the cell wall assembly geneftsI, the LPS biosynthesis genearnC, and the yersiniabactin uptake receptorfyuA.Diverse ESBL genes belonging to theblaCTX-M,blaSHV, andblaTEMfamilies were identified; these genes were found at varying numbers of loci and in variable numbers of copies across isolates. Analysis of ESBL flanking regions revealed diverse mobile elements that varied by ESBL type. Overall, our findings show that ST131 subclades C1 and C2 dominated and were stably maintained among patients in the same hospital and uncover possible signals of ongoing adaptation within the clade C ST131 lineage.
WITHDRAWN: Cross-species Myocardial Proteomics For Animal Models of Cardiometabolic Heart Failure With Preserved Ejection Fraction
Authors: Guo Alina , Yoo Edwin J. 
Published: December 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to insufficient sample size to make conclusions. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Assembly processes inferred from eDNA surveys of a pond metacommunity are consistent with known species ecologies
Authors: Cai Wang , Pichler Maximilian , Biggs Jeremy , Nicolet Pascale , Ewald Naomi , Griffiths Richard A. , Bush Alex , Leibold Mathew A. , Hartig Florian , Yu Douglas W. 
Published: December 2023

AbstractTechnological progress is enabling ecologists to create repeated, large-scale, structured, and standardised community surveys. However, it is unclear how best to extract information from these novel community data. We metabarcoded 48 vertebrate species from their eDNA in 320 ponds in England and applied the ‘internal-structure’ approach, which uses joint species distribution models to explain community compositions as the outcome of four metacommunity assembly processes: environmental filtering, dispersal, species interactions, and stochasticity. We find that the environment plays an important role in community assembly and that the inferred environmental preferences of species are consistent with their ecologies. We also infer negative biotic covariances between fish and amphibians, which is consistent with predator-prey interactions, and high spatial autocorrelation for the palmate newt, which is consistent with its hypothesised relictual distribution. Comparing sites in the metacommunity, environmentally and spatially distinctive sites are better explained by their environmental covariates and geographic locations, respectively, revealing sites where environmental filtering and dispersal limitation act more strongly. Furthermore, species belonging to different trait groups differ in how well environmental covariates, biotic covariances, and geographical locations explain their distributions. Overall, our results highlight the value of a modern interpretation of metacommunity ecology that embraces the fact that assembly processes differ between individual species and sites. We discuss how novel community data make feasible several study-design improvements that will strengthen the inference of metacommunity assembly processes from observational data.
Probabilistic clustering of cells using single-cell RNA-seq data
Authors: Saha Joy , Tanvir Ridwanul Hasan , Hassan Samee Md. Abul , Rahman Atif 
Published: December 2023

AbstractSingle-cell RNA sequencing is a modern technology for analyzing cellular heterogeneity. A key challenge is to cluster a heterogeneous sample of different cell types into multiple different homogeneous groups. Although there exist a number of clustering methods, they do not perform well consistently across various datasets. Moreover, most of them are not based on probabilistic approaches making it difficult to assess uncertainties in their results. Therefore, in spite of having large cell atlases, it is often quite difficult to map cells to types. In addition, many of the methods require prior knowledge such as marker gene information for each type. Also due to technological limitations, dropouts of gene expressions may occur in the data which is not taken into account in other methods. Here we present a probabilistic method named CellHorizon for clustering scRNA-seq data that is based on a generative model, handles dropouts and works without any prior marker gene information. Experiments reveal that our method outperforms current state-of-the-art methods overall on six gold standard datasets.