bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meditation in the third-person perspective modulates minimal self and heartbeat-evoked potentials
Authors: Yang Hang , Herbelin Bruno , Ngo Chuong , Vuarnesson Loup , Blanke Olaf 
Published: October 2024

AbstractExperienced meditation practitioners often report altered states of their sense of self, including decentering and distancing the self from the body and one’s current concerns. Altered states of the sense of self, such as disembodiment and distancing of the self from the body, have also been induced experimentally using virtual reality (VR) and linked neurally to heartbeat evoked potentials (HEPs). Whereas many studies investigated the related neural correlates of such decentering during meditation, none experimentally modulated the sense of self during meditation practice using VR nor determined the potentially associated behavioral changes of the sense of self. Here we determined HEPs and behavioral measures in 23 participants who performed a guided meditation practice in VR, either from a third-person (3PP) or first-person perspective (1PP) to modulate the sense of self. In the 3PP versus 1PP meditation condition, we report stronger sensations of detachment and disconnection, reduced salience of the perceived body boundary, and reduced self-identification with the body. HEP analysis revealed differential neural responses between conditions, characterized by a more negative HEP amplitude in the 3PP condition, associated with activation of the posterior cingulate cortex and medial prefrontal cortex. Leveraging a new VR-supported meditation platform and methods, these data link the sense of self in meditation practice to the neuroscience of the bodily self, based on subjective, behavioral, and neural measures.
Computational microbiology of soil organic matter mineralization: Use of the concept of curve skeleton to partition the 3D pore space in computed tomography images
Authors: Belghali Zakaria , Monga Olivier , Klai Mouad , Abdelwahed El Hassan , Druoton Lucie , Pot Valérie , Baveye Philippe C. 
Published: October 2024

AbstractRecent advances in 3D X-ray Computed Tomography (CT) sensors have stimulated research efforts to unveil the extremely complex micro-scale processes that control the activity of soil microorganisms. Classical methods for the numerical simulation of biological dynamics using meshes of voxels, such as the Lattice Boltzmann Method (LBM), tend to require long computation times. The use of more compact geometrical representations of the pore space can drastically decrease the computational cost of simulations. Recent research has introduced basic analytic volume primitives to define piece-wise approximations of the pore space to simulate drainage, diffusion, and microbial mineralization of organic matter in soils. Such approaches work well but a drawback is that they give rise to non-negligible approximation errors. In the present article, another alternative is proposed, where pore space is described by means of geometrically relevant connected subsets of voxels (regions) regrouped on the basis of the curve linear skeleton (3D medial axis). This curve skeleton has been adopted to characterize 3D shapes in various fields (e.g., medical imaging, material sciences, etc.) but the few publications that have used it in the context of soils, have dealt exclusively with the determination of pore throats. This technique is used mostly to describe shape and not to partition it into connected subsets. Here, the pore space is partitioned by using the branches of the curve skeleton, then an attributed relational graph is created in order to simulate numerically the microbial mineralization of organic matter, including the diffusion of by-products. This new representation can be used for graph-based simulations, which are different from voxel-based simulations.
G-quadruplexes in the RSV genome: potential anti-viral targets
Authors: Bose Debopriya , Panda Suman , Banerjee Nilanjan , Chatterjee Subhrangsu 
Published: October 2024

AbstractThe Rous sarcoma virus (RSV) is an onco-retrovirus that infects avian species such as the chicken (Gallus gallus). RSV is the first oncovirus to be described and the oncogenic activity of this virus is related to the expression of a tyrosine kinase that induces carcinogenic transformation. Interestingly, we have noted that the RSV genome contains various potential G4 forming sequences. Among these, two sequences located in the GAG and POL genes, respectively, show high G4 forming potential. Additionally, the SRC oncogene also harbours a putative G4 forming sequence. In this study, we have characterised the G4 formation and topology in these three loci in the RSV-DNA. We have found that these sequences form dynamic G4 structures in physiological conditions and such dynamicity may be associated with their cellular functions. Further, we have also established that these G4s are recognized by G4 interacting small-molecule ligands and the G4-stabilizing protein nucleolin. Binding of these ligands induces structural shifts in the G4 leading to change in structure and stability. Thus, the RSV-DNA G4s may be further studied as targets to control its infection and oncogenic effects.
Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and alter their functional properties
Authors: Mohan Harihar M. , Fernandez Martin G. , Huang Camellia , Lin Rita , Ryou Jaimie H. , Seyfried Donald , Grotewold Nikolas , Whiteley Alexandra M. , Barmada Sami J. , Basrur Venkatesha , Mosalaganti Shyamal , Paulson Henry L. , Sharkey Lisa M. 
Published: October 2024

ABSTRACTThe human genome is replete with sequences derived from foreign elements including endogenous retrovirus-like proteins of unknown function. Here we show that UBQLN2, a ubiquitin-proteasome shuttle factor implicated in neurodegenerative diseases, is regulated by the linked actions of two retrovirus-like proteins, RTL8 and PEG10. RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10. PEG10, a core component of stress granules, drives the recruitment of UBQLN2 to stress granules under various stress conditions, but can only do so when RTL8 is present. Changes in PEG10 levels further remodel the kinetics of stress granule disassembly and overall composition by incorporating select extracellular vesicle proteins. Within stress granules, PEG10 forms virus-like particles, underscoring the structural heterogeneity of this class of biomolecular condensates. Together, these results reveal an unexpected link between pathways of cellular proteostasis and endogenous retrovirus-like proteins.
Continuous integration of heading and goal directions guides steering
Authors: Crown Anthony M , Wu Annie H , Hofflander Lindsey , Barnea Gilad 
Published: October 2024

AbstractNavigating animals must integrate a diverse array of sensory cues into a single locomotor decision. Insects perform intricate navigational feats using a brain region termed the central complex in which an animal’s heading direction is transformed through several layers of circuitry to elicit goal-directed locomotion. These transformations occur mostly in the fan-shaped body (FB), a major locus of multi-sensory integration in the central complex. Key aspects of these sensorimotor computations have been extensively characterized by functional studies, leveraging the genetic tools available in the fruit fly. However, our understanding of how neuronal activity in the FB dictates locomotor behaviors during navigation remains enigmatic. Here, we manipulate the activity of two key neuronal populations that input into the FB–the PFNaand PFNdneurons–used to encode the direction of two complex navigational cues: wind plumes and optic flow, respectively. We find that flies presented with unidirectional optic flow steer along curved walking trajectories, but silencing PFNdneurons abolishes this curvature. We next use optogenetic activation to introduce a fictive heading signal in the PFNs to establish the causal relationship between their activity and steering behavior. Our studies reveal that the central complex guides locomotion by summing the PFN-borne directional signals and shifting movement trajectories left or right accordingly. Based on these results, we propose a model of central complex-mediated locomotion wherein the fly achieves fine-grained control of sensory-guided steering by continuously integrating its heading and goal directions over time.
Improved Methodology for Studying Postnatal Osteogenesis via Intramembranous Ossification in a Murine Bone Marrow Injury Model
Authors: Stetsiv Marta , Wan Matthew , Prabhu Shagun , Guzzo Rosa , Sanjay Archana 
Published: October 2024

ABSTRACTLong bone injuries heal through either endochondral or intramembranous bone formation pathways. Unlike the endochondral pathway that requires a cartilage template, the process of intramembranous ossification involves the direct conversion of skeletal stem and progenitor cells (SSPCs) into bone-forming osteoblasts. There are limited surgical methods to model this process in experimental mice. Here, we have improved upon a bone marrow injury model in mice to facilitate the study of bone repair via intramembranous ossification and to assess postnatal regulators of osteogenesis. This method is highly reproducible and user-friendly, and it allows temporal assessment of new bone formation in a short period (3-7 days post-injury) using µCT and frozen section histology. Furthermore, the contributions of SSPCs and mature osteoblasts can be readily assessed using a combination of fluorescent reporter mice and this intramembranous bone marrow injury model. In clinical contexts, intramembranous bone formation is relevant for healing critical size defects, stress fractures, cortical defects, trauma from tumor resections, and joint replacements.SUMMARYThe murine bone marrow injury model is a useful tool to study postnatal osteogenesis through intramembranous ossification. This simplified surgical protocol describes the bone marrow ablation procedure for downstream assessment of new bone formation and cellular responses following injury.
EpigeneticAgePipeline: an R package for comprehensive assessment of epigenetic age metrics from methylation microarrays
Authors: Rayevskiy Stanislav , Le Quinn , Nguyen Julia , Chen Steven Q. , Castellani Christina A. 
Published: October 2024

AbstractSummaryEpigenetic age is a biological age estimation that is based off nuclear DNA methylation patterns. As an individual ages, methylation sites change in a predictable manner, allowing for the generation of epigenetic age clocks. EpigeneticAgePipeline is an R package that aims to provide a straightforward, out-of-the-box solution for measuring epigenetic age estimates (Horvath, skinHorvath, Hannum, PhenoAge/Levine, GrimAge), as well as two epigenetic age acceleration measures (DunedinPACE, GrimAge Acceleration). Further, EpigeneticAgePipeline imputes cell counts, as well as performs statistical analyses including principal component analysis, normalization, and generation of linear model-based residuals. The pipeline supports Illumina Infinium methylation microarray formats, including HumanMethylation27, HumanMethylation450, and HumanMethylationEPIC. Our package offers an all-in-one solution to generate epigenetic age estimates from input IDAT files or preprocessed methylation beta values.AvailabilityEpigeneticAgePipeline is implemented in R (3.5 or greater) and available on GitHub athttps://github.com/CastellaniLab/EpigeneticAgePipelineSupplementary InformationPDF file submitted along with manuscript.
Idiosyncrasy and generalizability of contraceptive- and hormone-related functional connectomes across the menstrual cycle
Authors: Bottenhorn Katherine L. , Salo Taylor , Jacobs Emily G. , Pritschet Laura , Taylor Caitlin , Herting Megan M. , Laird Angela R. 
Published: October 2024

AbstractNeuroendocrinology has received little attention in human neuroscience research, resulting in a dearth of knowledge surrounding potent and dynamic modulators of cognition and behavior, as well as brain structure and function. This work addresses one such phenomenon by studying functional connectomics related to ovarian hormone fluctuations throughout the adult menstrual cycle. To do so, we used functional magnetic resonance imaging (fMRI) and hormone assessments from two dense, longitudinal datasets to assess variations in functional connectivity with respect to endogenous and exogenous endocrine factors throughout the menstrual cycle. First, we replicated prior findings that common, group-level and individual specific factors have similar relative contributions to functional brain network organization. Second, we found widespread connectivity related to hormonal contraceptive (HC) use, in addition to sparser estradiol- and progesterone-related connectivity, and differential generalizability of these subnetworks that suggests progestin-specific impacts on functional connectivity in HC users. These results provide novel insight into within-individual changes in brain organization across the menstrual cycle and the extent to which these changes are shared between individuals, illuminating understudied phenomena in reproductive health and important information for all neuroimaging studies that include participants who menstruate.Author SummaryEndocrine modulation of brain function across the menstrual cycle is poorly understood. Human neuroimaging research on the menstrual cycle has long relied on group- and or coarse, within-individual cycle stage-differences, overlooking considerable individual differences in brain organization, the menstrual cycle, and hormone concentrations. Here, we take a multi-dataset approach to identify idiosyncratic contraceptive- and hormone-related functional connectivity from within-individual neuroendocrine dynamics and then test the generalizability of this connectivity to other individuals. In doing so, we identified idiosyncratic hormone-responsive subnetworks that are somewhat generalizable to other individuals, though this generalizability is complicated by hormonal contraceptive use, potentially reflecting differential connectivity between contraceptive formulations. Thus, this work illuminates individual similarities and differences in neuroendocrine dynamics across the menstrual cycle.
HT SpaceM: A High-Throughput and Reproducible Method for Small-Molecule Single-Cell Metabolomics
Authors: Delafiori Jeany , Shahraz Mohammed , Eisenbarth Andreas , Hilsenstein Volker , Drotleff Bernhard , Bailoni Alberto , Wadie Bishoy , Ekelöf Måns , Mattausch Alexander , Alexandrov Theodore 
Published: October 2024

SummarySingle-cell metabolomics promises to resolve metabolic cellular heterogeneity, yet current methods struggle with detecting small molecules, throughput, and reproducibility. Addressing these gaps, we developed HT SpaceM, a high-throughput single-cell metabolomics method with novel cell preparation, custom glass slides, small-molecule MALDI imaging mass spectrometry protocol, and batch processing. We propose a unified framework covering essential data analysis steps including quality control, characterization, differential analysis, structural validation and functional analysis. Interrogating human HeLa and mouse NIH3T3 cells, we detected 73 diverse small-molecule metabolites validated by bulk LC-MS/MS, achieving high reproducibility across wells and slides. Interrogating nine NCI-60 cancer cells and HeLa, we identified cell-type markers in small subpopulations. Functional analysis revealed overrepresented metabolic pathways, co-abundant metabolites, and metabolic hubs. We demonstrate the ability of SCM to analyze over 120,000 cells from over 112 samples, and provide guidance to interpret single-cell metabolic heterogeneity, revealing metabolic insights beyond population averages.
Connexin 43 mediated monocyte mitochondrial transfer prevents cisplatin induced sensory neurodegeneration
Authors: Owen Rebecca , Corbett Jack , Paul-Clark Mark , Hulse Richard Philip 
Published: October 2024

AbstractPlatinum based chemotherapeutics including cisplatin are front-line treatments for paediatric and adult cancer. Despite advancements in medical interventions, chemotherapy-induced peripheral sensory neuropathy is a common adverse health related complication that can persist for the long-term and impacts upon an individual’s quality of life. Recently, the causes of chemotherapy induced sensory neurodegeneration has been linked to sensory neuronal mitochondrial dysfunction. Here this study investigated how monocytic mitochondria donation to recipient cisplatin damaged dorsal root ganglia (DRG) sensory neurons prevented platinum-based chemotherapy-induced sensory neurotoxicity. Neuronal cell line, SH-SY5Y, or mouse DRG sensory neurons were treated with either vehicle or cisplatin, and co-cultured with mitotracker-labelled THP1 monocytes. Cisplatin induced dysmorphic mitochondria and diminished oxidative phosphorylation dependent energy production in cisplatin treated dorsal root ganglia sensory neurons. DRG sensory neurons exposed to cisplatin were recipients of monocyte mitochondria indicated by increased intracellular mitotracker fluorescent labelling. Mitochondrial transfer to sensory neurons was neuroprotective, preventing neurite loss and sensory neuronal apoptosis. Vehicle treated DRG sensory neurons did not demonstrate significant mitochondrial uptake. Furthermore, cisplatin induced mitochondrial transfer was prevented by pharmacological inhibition of gap junction protein, connexin 43. Connexin 43 inhibition led to reduced neuroprotective capacity via mitochondrial transfer. These findings demonstrate that monocytic mitochondria transfer to DRG sensory neurons damaged by cisplatin, is dependent upon gap junction intercellular communication to promote sensory neuronal survival. This novel process in sensory neuronal protection is a potential novel therapeutic intervention for alleviating neuropathic pain in individuals treated for cancer.
Design of Parameter Intervals to Meet Steady-State Specifications in Biomolecular Circuits using Interval Analysis
Authors: Prakash Rudra , Janardhanan S. , Sen Shaunak 
Published: October 2024

AbstractIt is often desired, in the analysis or the design of biomolecular circuits, to search for parameters that satisfy certain specifications, such as on the number of the steady states or on their magnitudes. These problems are challenging because of the presence of multiple parameters, the nonlinear mapping between the parameters and the steady states, as well as the specifications themselves, such as when multiple steady states are desired. Typically, exact analytical solutions are limited and numerical approaches, if they converge, may not capture all solutions. We used Interval Analysis versions of Bisection and Constraint Propagation to obtain rigorous and guaranteed estimates of circuit parameters for the design problem. We established criteria that rule out the existence of design solutions in a given parameter space. We presented algorithms to rigorously bound all solutions and developed variants that enclosed the solutions as accurately as required. These theoretical results were illustrated on benchmark feedback and feedforward circuits. These results should aid in the analysis and design of biomolecular circuits as well as in other contexts with similar modelling frameworks. The rigorous nature of the results may be particularly useful for resource optimization and safety criticality in synthetic biology applications, such as in therapeutic applications and drug delivery.
Mettl5coordinates protein production and degradation of PERIOD to regulate sleep inDrosophila
Authors: Wu Xiaoyu , Yang Xingzhuo , Fu Tiantian , Rong Yikang S. , Du Juan 
Published: October 2024

SummarySleep is crucial for animal physiology, primarily governed by the brain, and disruptions are prevalent in various brain disorders.Mettl5, associated with intellectual disability (ID) often accompanied by sleep disturbances, remains poorly understood in its role causing these disorders. Previous research demonstrated that Mettl5 forms a complex with Trmt112, influencing rRNA methylation. In our study, we explored sleep phenotypes due toDrosophila Mettl5mutations. Rescue experiments pinpointedMettl5’s predominant role in neurons and glia marked byMettl5-Gal4 in sleep regulation. Notably, aTrmt112mutation mirrored these sleep disturbances, implicating translational regulation via the Mettl5/Trmt112 complex. Subsequent RNA-seq and Ribo-seq analyses unveiled downstream events fromMettl51bpmutations, revealing altered expression levels of proteasome components and Clock genes. Rescue experiments confirmed that the net increased PERIOD protein is responsible for the sleep phenotype. This investigation sheds light on ribosome, clock genes, and proteasome interplay in sleep regulation, underscoring protein synthesis and degradation’s integrative role. These findings could potentially provide an example ofin vivostudy of the function of rRNA methylation, expand our understanding of the role of protein homeostasis in sleep and inspire explanations on the ID related sleep phenotypes.
WITHDRAWN: MIRAGE: a Bayesian rare variant association analysis method incorporating functional information of variants
Authors: Han Shengtong , Sun Xiaotong , Sloofman Laura , Satterstrom F. Kyle , Wang Gao , Liang Lifan , Knoblauch Nicholas , Zhao Siming , Liu Yuwen , Sheng Wenhui , Nguyen Hoang T. , He Xin 
Published: October 2024

Withdraw StatementThe authors have withdrawn this manuscript due to a duplicate submission and request that it not be cited as a reference for ongoing projects. For further inquiries, please contact the corresponding author.Details regarding this project are available athttps://www.biorxiv.org/content/10.1101/828061v1.article-info.
Irx3/5define the cochlear sensory domain and regulate vestibular and cochlear sensory patterning in the mammalian inner ear
Authors: Liu Yuchen , Qin Tianli , Weng Xin , Leung Bernice , Hei So Karl Kam , Wang Boshi , Feng Wanying , Marsolais Alexander , Josselyn Sheena , Huang Pingbo , Fritzsch Bernd , Hui Chi-Chung , Sham Mai Har 
Published: October 2024

AbstractThe mammalian inner ear houses the vestibular and cochlear sensory organs dedicated to sensing balance and sound, respectively. These distinct sensory organs arise from a common prosensory region, but the mechanisms underlying their divergence remain elusive. Here, we showed that two evolutionarily conserved homeobox genes,Irx3andIrx5, are required for the patterning and segregation of the saccular and cochlear sensory domains, as well as for the formation of auditory sensory cells.Irx3/5were highly expressed in the cochlea, their deletion resulted in a significantly shortened cochlea with a loss of the ductus reuniens that bridged the vestibule and cochlea. Remarkably, ectopic vestibular hair cells replaced the cochlear non-sensory structure, the Greater Epithelial Ridge. Moreover, most auditory sensory cells in the cochlea were transformed into hair cells of vestibular identity, with only a residual organ of Corti remaining in the mid-apical region ofIrx3/5double knockout mice. Conditional temporal knockouts further revealed thatIrx3/5are essential for controlling cochlear sensory domain formation before embryonic day 14. Our findings demonstrate that Irx3/5 regulate the patterning of vestibular and cochlear sensory cells, providing insights into the separation of vestibular and cochlear sensory organs during mammalian inner ear development.