bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONDITIONALLY MUTANT ANIMAL MODEL FOR INVESTIGATING THE INVASIVE TROPHOBLAST CELL LINEAGE
Authors: Iqbal Khursheed , Nixon Brandon , Crnkovich Benjamin , Dominguez Esteban M. , Moreno-Irusta Ayelen , Scott Regan L. , Vu Ha T.H. , Tuteja Geetu , Vivian Jay L. , Soares Michael J. 
Published: August 2023

ABSTRACTPlacental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade into the uterus where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome editing techniques. In this investigation, we generated a conditional rat model targeting the invasive trophoblast cell lineage. Prolactin family 7, subfamily b, member 1 (Prl7b1) is uniquely and abundantly expressed in the rat invasive trophoblast cell lineage. Disruption ofPrl7b1did not adversely affect placental development. We demonstrated that thePrl7b1locus could be effectively used to drive the expression of Cre recombinase in invasive trophoblast cells. Our rat model represents a new tool for investigating candidate genes contributing to the regulation of invasive trophoblast cells and their contributions to trophoblast-guided uterine spiral artery remodeling.
Predicting brain activity using Transformers
Authors: Adeli Hossein , Minni Sun , Kriegeskorte Nikolaus 
Published: August 2023

AbstractThe Algonauts challenge [Gifford et al., 2023] called on the community to provide novel solutions for predicting brain activity of humans viewing natural scenes. This report provides an overview and technical details of our submitted solution. We use a general transformer encoder-decoder model to map images to fMRI responses. The encoder model is a vision transformer trained using self-supervised methods (DINOv2). The decoder uses queries corresponding to different brain regions of interests (ROI) in different hemispheres to gather relevant information from the encoder output for predicting neural activity in each ROI. The output tokens from the decoder are then linearly mapped to the fMRI activity. The predictive success (challenge score: 63.5229, rank 2) suggests that features from self-supervised transformers may deserve consideration as models of human visual brain representations and shows the effectiveness of transformer mechanisms (self and cross-attention) to learn the mapping from features to brain responses. Code is available in thisgithub repository.
Multi-day Neuron Tracking in High Density Electrophysiology Recordings using EMD
Authors: Yuan Augustine(Xiaoran) , Colonell Jennifer , Lebedeva Anna , Okun Michael , Charles Adam S. , Harris Timothy D. 
Published: August 2023

AbstractAccurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from one to 47 days, with an 84% average recovery rate.
A reverse-central-dogma pathway underlies ribosome-antibiotic efficacy and accelerates resistance evolution
Authors: Zheng Yayun , Chai Ruochen , Xu Zeqi , He Yihui , Shen Ping , Liu Jintao , Wang Tianmin 
Published: August 2023

Withdrawal StatementThis manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. 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.
A single-cell transcriptomic analysis of the mouse hippocampus after voluntary exercise
Authors: Methi Aditi , Islam Md Rezaul , Kaurani Lalit , Sakib M Sadman , Krüger Dennis M. , Burkhardt Susanne , Liebetanz David , Fischer André 
Published: August 2023

AbstractExercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after four weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation ofPrdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-κB, Wnt/β-catenin, Notch, retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important resource dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline.
Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model
Authors: Xue Yunlu , Zhou Yimin , Cepko Constance L. 
Published: August 2023

AbstractRetinitis pigmentosa (RP) is a prevalent inherited retinal degenerative disease worldwide, affecting 1 in 4,000 people. The disease is characterized by an initial loss of night vision followed by a loss of daylight and color vision. Many of the RP disease genes are expressed in the rod photoreceptors, the cell type that initiates dim light vision. Following loss of rods, the cone photoreceptors, which initiate daylight vision, also are affected and can die leading to total loss of vision. The reasons for loss of cone vision are not entirely clear, but appear to be due to loss of the rods. Previously we showed that overexpressing Txnip, an α-arrestin protein, in mouse models of RP using AAV gene therapy prolonged the survival of RP cones (Xue et al., 2021). At least part of the mechanism for cone survival was a switch in the fuel source, from glucose to lactate. In addition, the mitochondria of cones were both morphologically and functionally improved by delivery of Txnip. We have gone on to test several alleles of Txnip for the ability to prolong cone survival inrd1, a mouse model of RP. In addition, proteins that bind to Txnip and/or have homology to Txnip were tested. Five different deletion alleles of Txnip were expressed in cones or the retinal pigmented epithelium (RPE). Here we show that the C-terminal half of Txnip (149-397aa) is sufficient to remove GLUT1 from the RPE cell surface, and improvedrd1cone survival when expressed specifically in the RPE. Overexpressing Arrdc4, an α-arrestin that shares 60% similar protein sequence to Txnip, reducedrd1cone survival. Reduction of the expression of HSP90AB1, a protein that interacts with Txnip and regulates metabolism, improved the survival ofrd1cones alone and was additive for cone survival when combined with Txnip. However, full length Txnip with a single amino acid change, C247S, as we tested in our original study, remains the most highly efficacious form of the gene for cone rescue. The above observations suggest that only a subset of the hypothesized and known activities of Txnip play a role in promoting RP cone survival, and that the activities of Txnip in the RPE differ from those in cone photoreceptors.
Comparative genomics of two closely related coral species with different spawning seasons reveals genomic regions possibly associated with gametogenesis
Authors: Takahashi-Kariyazono Shiho , Iguchi Akira , Terai Yohey 
Published: August 2023

AbstractMarine invertebrates release their gametes at an optimal time to produce the next generation. In reef-building scleractinian corals, synchronous spawning is essential for reproductive success. Molecular mechanisms of scleractinian gametogenesis have been studied; however, the mechanism by which coral gametes mature at specific times has yet to be discovered. The present study focused on twoAcroporaspecies with different spawning seasons. In Okinawa, Japan,Acropora digitiferaspawns from May to June, whereasAcroporasp. 1 spawns in August. Comparative genomic analyses revealed that 39 candidate genes are differentiated between the two species, suggesting a possible association with timing of gametogenesis. Among candidate genes, we identified anAcroporasp. 1-specific amino acid change in geneWDR59, one of the components of a mTORC1 activator, GATOR2. Since regulation of gametogenesis by mTORC1 is widely conserved among eukaryotes, the difference in timing of gamete maturation observed in the twoAcroporaspecies may be caused by a substitution in WDR59 that slightly affects timing of mTORC1 activation via GATOR2. In addition, this substitution may lead to reproductive isolation between the two species, due to different spawning periods. Thus, we propose that A. digitifera and Acropora sp. 1 species pair is an effective model for studying coral speciation and understanding the molecular mechanisms that control coral spawning timing.Significance statement (required)For successful coral reproduction, conspecific corals must spawn synchronously. Gamete production initiates coral spawning. Regulation of gamete maturation by a protein complex, mTORC1, is widely conserved among organisms, but little is known about it in cnidarians. In this study, we analyzed genomes of two closely relatedAcroporaspecies with different spawning months, May/June and August. Our analyses revealed that 39 genes are genetically differentiated between the two species. One of these is a component of mTORC1 activator, suggesting that this gene may be associated with the difference in spawning times of these two species.
Mechanical forces and ligand-binding modulatePseudomonas aeruginosaPilY1 mechanosensitive protein
Authors: Cao-Garcia Francisco J. , Walker Jane E. , Board Stephanie , Alonso-Caballero Alvaro 
Published: August 2023

AbstractBacteria initiate colonization and biofilm formation in response to mechanical cues caused by surface proximity. The protein PilY1 has been proposed as a key actor mediating mechanosensing. PilY1 is a calcium and integrin-binding protein with additional roles in host adhesion and functional regulation of the type IV pili (T4P), the appendages involved in twitching motility, and various aspects of the surface-associated life of bacteria. Due to its extracellular location and involvement in several surface processes, PilY1 is exposed to mechanical forces that could modulate its different roles. Herein, we explore the effect of mechanical forces and ligand binding on the conformational dynamics of the PilY1 C-terminal domain. Our single-molecule approach demonstrates that PilY1 acts as a ligand-modulated force sensor. At high forces, PilY1 unfolding occurs through a hierarchical sequence of intermediates. When calcium is bound to its cognate site linked to T4P regulation, there is a long-range mechanical stabilization affecting several PilY1 domains, which ensures the structural integrity of the protein. In the low-force regime, the integrin-binding domain of PilY1 exhibits calcium-tuned force sensitivity and conformational dynamics akin to those of mechanosensor proteins. Integrin binding to this domain occurs under force, inducing a shortening of its unfolded extension. Our findings suggest that the roles of the PilY1 C-terminal domain are force and ligand-modulated, which could entail a mechanical-based compartmentalization of its functions.
Determining the structure of protein-bound ceramides, essential lipids for skin barrier function
Authors: Ohno Yusuke , Nakamura Tetsuya , Iwasaki Takafumi , Katsuyama Akira , Ichikawa Satoshi , Kihara Akio 
Published: August 2023

SummaryProtein-bound ceramides, specialized ceramides covalently bound to corneocyte surface proteins, are essential for skin permeability barrier function. However, their exact structure and target amino acid residues are unknown. Here, we found that epoxy-enone (EE) ceramides, precursors of protein-bound ceramides, as well as their synthetic analog, formed stable conjugates only with Cys among nucleophilic amino acids. NMR spectroscopy revealed that the β-carbon of the enone was attached by the thiol group of Cys via a Michael addition reaction. We confirmed the presence of Cys-bound EE ceramides in mouse epidermis by mass spectrometry analysis of protease-digested epidermis samples. EE-ceramides were reversibly released from protein-bound ceramides via sulfoxide elimination. We found that protein-bound ceramides with reversible release properties accounted for approximately 60% of total protein-bound ceramides, indicating that Cys-bound EE ceramides are the predominant protein-bound ceramides. Our findings provide clues to the molecular mechanism of skin barrier formation by protein-bound ceramides.HighlightsEpoxy-enone (EE) ceramides form stable conjugates with Cys.Cys binds to the β-carbon of the enone via a Michael addition reaction.Cys-bound EE ceramides exist in the mouse epidermis.Cys-bound EE ceramides are the predominant protein-bound ceramides.In BriefProtein-bound ceramides are specialized ceramides essential for skin permeability barrier function. In the present study, we determined the exact structure of protein-bound ceramides as Cys-bound epoxy-enone ceramides where the β-carbon of the epoxy-enone ceramides is attached by Cys residues of corneocyte surface proteins via a Michael addition reaction.
Comparing full variation profile analysis with the conventional consensus method in SARS-CoV-2 phylogeny
Authors: Nóra Fiam Regina , István Csabai , Norbert Solymosi 
Published: August 2023

ABSTRACTThis study proposes a novel approach to studying SARS-CoV-2 virus mutations through sequencing data comparison. Traditional consensus-based methods, which focus on the most common nucleotide at each position, might overlook or obscure the presence of low-frequency variants. Our method, in contrast, retains all sequenced nucleotides at each position, forming a genomic matrix. Utilizing simulated short reads from genomes with specified mutations, we contrasted our genomic matrix approach with the consensus sequence method. Our matrix methodology accurately reflected the known mutations and true compositions, demonstrating its efficacy in understanding the sample variability and their interconnections. Further tests using real data from GISAID and NCBI-SRA confirmed its reliability and robustness. As we see, the genomic matrix approach offers a more accurate representation of the viral genomic diversity, thereby providing superior insights into virus evolution and epidemiology. Future application recommendations are provided based on our observed results.
Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence
Authors: Sun Siyu , Tranchina Daniel , Gresham David 
Published: August 2023

AbstractCells arrest growth and enter a quiescent state upon nutrient deprivation. However, the molecular processes by which cells respond to different starvation signals to regulate exit from the cell division cycle and initiation of quiescence remains poorly understood. To study the role of protein expression and signaling in quiescence we combined temporal profiling of the proteome and phosphoproteome using stable isotope labeling with amino acids in cell culture (SILAC) inSaccharomyces cerevisiae(budding yeast). We find that carbon and phosphorus starvation signals activate quiescence through largely distinct remodeling of the proteome and phosphoproteome. However, increased expression of mitochondrial proteins is associated with quiescence establishment in response to both starvation signals. Deletion of the putative quiescence regulatorRIM15, which encodes a serine-threonine kinase, results in reduced survival of cells starved for phosphorus and nitrogen, but not carbon. However, we identified common protein phosphorylation roles for RIM15 in quiescence that are enriched for RNA metabolism and translation. We also find evidence for RIM15-mediated phosphorylation of some targets, including IGO1, prior to starvation consistent with a functional role for RIM15 in proliferative cells. Finally, our results reveal widespread catabolism of amino acids in response to nitrogen starvation, indicating widespread amino acid recycling via salvage pathways in conditions lacking environmental nitrogen. Our study defines an expanded quiescent proteome and phosphoproteome in yeast, and highlights the multiple coordinated molecular processes at the level of protein expression and phosphorylation that are required for quiescence.
A graded neonatal mouse model of necrotizing enterocolitis demonstrates that mild enterocolitis is sufficient to activate microglia and increase cerebral cytokine expression
Authors: Sha Cuilee , Van Brunt Trevor , Kudria Jacob , Schmidt Donna , Yurovsky Alisa , Bandovic Jela , Giarrizzo Michael , Lin Joyce , Tsirka Styliani-Anna , Bialkowska Agnieszka B , Wollmuth Lonnie , Speer Esther , Hsieh Helen 
Published: August 2023

AbstractBackgroundNecrotizing enterocolitis (NEC) is an inflammatory gastrointestinal process that afflicts approximately 10% of preterm infants born in the United States each year, with a mortality rate of 30%. NEC severity is graded using Bell’s classification system, from stage I mild NEC to stage III severe NEC. Over half of NEC survivors present with neurodevelopmental impairment during adolescence, a long-term complication that is poorly understood but can occur even after mild NEC. Although multiple animal models exist, none allow the experimenter to control nor represent the gradient of symptom severities seen in NEC patients. We bridge this knowledge gap by developing a graded murine model of NEC and studying its relationship with neuroinflammation across a range of NEC severities.MethodsPostnatal day 3 (P3) C57BL/6 mice were fed a formula containing different concentrations (0% control, 0.25%, 1%, 2%, and 3%) of dextran sodium sulfate (DSS). P3 mice were fed every 3 hours for 72-hours. We collected data on weight gain and behavior (activity, response, body color) during feeding. At the end of the experiment, we collected tissues (intestine, liver, plasma, brain) for immunohistochemistry, immunofluorescence, and cytokine and chemokine analysis.ResultsThroughout NEC induction, mice fed higher concentrations of DSS died sooner, lost weight faster, and became sick or lethargic earlier. Intestinal characteristics (dilation, color, friability) were worse in mice fed with higher DSS concentrations. Histology revealed small intestinal disarray among mice fed all DSS concentrations, while higher DSS concentrations resulted in reduced small intestinal cellular proliferation and increased hepatic and systemic inflammation. In the brain, IL-2, G-CSF, and CXCL1 concentrations increased with higher DSS concentrations. Although the number of neurons and microglia in the CA1 hippocampal region did not differ, microglial branching was significantly reduced in DSS-fed mice.ConclusionWe characterize a novel graded model of NEC that recapitulates the full range of NEC severities. We show that mild NEC is sufficient to initiate neuroinflammation and microglia activation. This model will facilitate studies on the neurodevelopmental effects of NEC.
Ranking and serial thinking: A geometric solution
Authors: Di Antonio Gabriele , Raglio Sofia , Mattia Maurizio 
Published: August 2023

AbstractA general mathematical description of the way the brain encodes ordinal knowledge of sequences is still lacking. Coherently with the well-established idea of mixed selectivity in high-dimensional state spaces, we conjectured the existence of a linear solution for serial learning tasks. In this theoretical framework, the neural representation of the items in a sequence are read out as ordered projections along a suited “geometric” mental line learnedviaclassical conditioning (delta rule learning). We show that the derived model explains all the behavioral effects observed in humans and other animal species performing the transitive inference task in presence of noisy sensory information and stochastic neural activity. This result is generalized to the case of recurrent neural networks performing motor decision, where the same geometric mental line is learned showing a tight correlation with the motor plan of the responses. Network activity is then eventually modulated according to the symbolic distance of presented item pairs, as observed in associative cortices of nonhuman primates. Serial ordering is thus predicted to emerge as a linear mapping between sensory input and behavioral output, highlighting a possible pivotal role of motor-related associative cortices in the transitive inference task.
Correlative single-cell hard X-ray tomography and X-ray fluorescence imaging
Authors: Lin Zihan , Zhang Xiao , Nandi Purbasha , Lin Yuewei , Wang Liguo , Chu Yong , Paape Timothy , Yang Yang , Xiao Xianghui , Liu Qun 
Published: August 2023

AbstractX-ray tomography (XRT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XRT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XRT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.