bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the impact of whole genome duplication on transposable element evolution in ray-finned fishes
Authors: Mallik Rittika , Wcisel Dustin J. , Near Thomas J. , Yoder Jeffrey A. , Dornburg Alex 
Published: December 2023

AbstractTransposable elements (TEs) can make up more than 50% of any given vertebrate’s genome, with substantial variability in TE composition among lineages. TE variation is often linked to changes in gene regulation, genome size, and speciation. However, the role that genome duplication events have played in generating abrupt shifts in the composition of the mobilome over macroevolutionary timescales remains unclear. We investigated the degree to which the teleost genome duplication (TGD) shaped the diversification trajectory of the ray-finned fish mobilome. We integrate a new high coverage genome ofPolypterus bichirwith data from over 100 publicly available actinopterygian genomes to assess the macroevolutionary implications of genome duplication events on TE evolution. Our results provide no evidence for a substantial shift in mobilome composition following the TGD event. Instead, the diversity of the actinopterygian mobilome appears to have been shaped by a history of lineage specific shifts in composition that are not correlated with commonly evoked drivers of diversification such as body size, water column usage, or latitude. Collectively, these results provide a new perspective on the early diversification of the actinopterygian mobilome and suggest that historic ploidy events may not necessarily catalyze bursts of TE diversification and innovation.
Large scale, simultaneous, chronic neural recordings from multiple brain areas
Authors: Melin Maxwell D , Khanal Anup , Vasquez Marvin , Ryan Michael B , Churchland Anne K , Couto Joao 
Published: December 2023

AbstractUnderstanding how brain activity is related to animal behavior requires measuring multi-area interactions on multiple timescales. However, methods to perform chronic, simultaneous recordings of neural activity from many brain areas are lacking.Here, we introduce a novel approach for independent chronic probe implantation that enables flexible, simultaneous interrogation of neural activity from many brain regions during head restrained or freely moving behavior. The approach, that we calledindie(independentdovetail implants forelectrophysiology), enables repeated retrieval and reimplantation of probes. The chronic implantation approach can be combined with other modalities such as skull clearing for cortex wide access and optogenetics with optic fibers. Using this approach, we implanted 6 probes chronically in one hemisphere of the mouse brain.The implant is lightweight, allows flexible targeting with different angles, and offers enhanced stability. Our approach broadens the applications of chronic recording while retaining its main advantages over acute recordings (superior stability, longitudinal monitoring of activity and freely moving interrogations) and provides an appealing venue to study processes not accessible by acute methods, such as the neural substrate of learning across multiple areas.
Open-ST: High-resolution spatial transcriptomics in 3D
Authors: Schott Marie , León-Periñán Daniel , Splendiani Elena , Strenger Leon , Licha Jan Robin , Pentimalli Tancredi Massimo , Schallenberg Simon , Alles Jonathan , Tagliaferro Sarah Samut , Boltengagen Anastasiya , Ehrig Sebastian , Abbiati Stefano , Dommerich Steffen , Pagani Massimiliano , Ferretti Elisabetta , Macino Giuseppe , Karaiskos Nikos , Rajewsky Nikolaus 
Published: December 2023

AbstractSpatial transcriptomics (ST) methods have been developed to unlock molecular mechanisms underlying tissue development, homeostasis, or disease. However, there is a need for easy-to-use, high-resolution, cost-efficient, and 3D-scalable methods. Here, we report Open-ST, a sequencing-based, open-source experimental and computational resource to address these challenges and to study the molecular organization of tissues in 3D. In mouse brain, Open-ST captured transcripts at subcellular resolution and reconstructed cell types. In primary tumor and patient-matched healthy/metastatic lymph nodes, Open-ST captured the diversity of immune, stromal and tumor populations in space. Distinct cell states were organized around cell-cell communication hotspots in the tumor, but not the metastasis. Strikingly, the 3D reconstruction and multimodal analysis of the metastatic lymph node revealed spatially contiguous structures not visible in 2D and potential biomarkers precisely at the 3D tumor/lymph node boundary. We anticipate Open-ST to accelerate the identification of spatial molecular mechanisms in 2D and 3D.
Cellular Senescence Impairs Tendon Extracellular Matrix Remodeling in Response to Mechanical Unloading
Authors: Stowe Emma J. , Keller Madelyn R. , Connizzo Brianne K. 
Published: December 2023

AbstractMusculoskeletal injuries, including tendinopathies, present a significant clinical burden for aging populations. While the biological drivers of age-related declines in tendon function are poorly understood, it is well accepted that dysregulation of extracellular matrix (ECM) remodeling plays a role in chronic tendon degeneration. Senescent cells, which have been associated with multiple degenerative pathologies in musculoskeletal tissues, secrete a highly pro-inflammatory senescence-associated secretory phenotype (SASP) that has potential to promote ECM breakdown. However, the role of senescent cells in the dysregulation of tendon ECM homeostasis is largely unknown. To assess this directly, we developed anin vitromodel of induced cellular senescence in murine tendon explants. This novel technique enables us to study the isolated interactions of senescent cells and their native ECM without interference from age-related systemic changes. We document multiple biomarkers of cellular senescence in induced tendon explants including cell cycle arrest, apoptosis resistance, and SASP production. We then utilize thisin vitrosenescence model to compare the ECM remodeling response of young, naturally aged, and senescent tendons to an altered mechanical stimulus. We found that both senescence and aging independently led to alterations in ECM-related gene expression, reductions in protein synthesis, and tissue compositional changes. Furthermore, MMP activity was sustained, thus shifting the remodeling balance of aged and senescent tissues towards degradation over production. Together, this demonstrates that cellular senescence plays a role in the altered mechano-response of aged tendons and likely contributes to poor clinical outcomes in aging populations.
Functional mapping of the somatosensory cortex using noninvasive fMRI and touch in awake dogs
Authors: Guran C.-N. Alexandrina , Boch Magdalena , Sladky Ronald , Lonardo Lucrezia , Karl Sabrina , Huber Ludwig , Lamm Claus 
Published: December 2023

AbstractDogs are increasingly used as a model for neuroscience due to their ability to undergo functional MRI fully awake and unrestrained, after extensive behavioral training. Still, we know rather little about dogs’ basic functional neuroanatomy, including how basic perceptual and motor functions are localized in their brains. This is a major shortcoming in interpreting activations obtained in dog fMRI. The aim of this preregistered study was to localize areas associated with somatosensory processing. To this end, we touched N = 22 dogs undergoing fMRI scanning on their left and right flanks using a wooden rod. We identified activation in anatomically defined primary and secondary somatosensory areas (SI and SII), lateralized to the contralateral hemisphere depending on the side of touch, as well as activations, beyond an anatomical mask of SI and SII, in the cingulate cortex, right cerebellum and vermis, and the Sylvian gyri. These activations may partly relate to motor control (cerebellum, cingulate), but also potentially to higher-order cognitive processing of somatosensory stimuli (rostral Sylvian gyri), and the affective aspects of the stimulation (cingulate). We also found evidence for individual side biases in a vast majority of dogs in our sample, pointing at functional lateralization of somatosensory processing. These findings not only provide further evidence that fMRI is suited to localize neuro-cognitive processing in dogs in vivo, but also expand our understanding of touch processing in mammals, beyond classically defined primary and secondary somatosensory cortices.Significance StatementTo understand brain function and evolution, it is necessary to look beyond the human lineage. This study provides insights into the engagement of brain areas related to somatosensation using whole-brain non-invasive neuroimaging of trained, non-sedated, and unrestrained pet dogs. It showcases again the usefulness of non-invasive methods, in particular fMRI, for investigating brain function and advances the mapping of brain functions in dogs; using this non-invasive approach without sedation, we are able to identify previously unknown potential higher-order processing areas and offer a quantification of touch processing lateralization.
Reliability of task-based fMRI in the dorsal horn of the human spinal cord
Authors: Dabbagh Alice , Horn Ulrike , Kaptan Merve , Mildner Toralf , Müller Roland , Lepsien Jöran , Weiskopf Nikolaus , Brooks Jonathan C.W. , Finsterbusch Jürgen , Eippert Falk 
Published: December 2023

AbstractThe application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across two consecutive days in 40 healthy volunteers. We assessed the test-retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat pain stimuli (1s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, bothβ-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat pain stimuli as short as one second are able to evoke a robust and spatially specific BOLD response, which is however strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.
Image-based computational fluid dynamics to compare two mitral valve reparative techniques for the prolapse
Authors: Bennati Lorenzo , Puppini Giovanni , Giambruno Vincenzo , Luciani Giovanni Battista , Vergara Christian 
Published: December 2023

AbstractObjectiveNowadays, the treatment of mitral valve prolapse involves two distinct repair techniques: chordal replacement (Neochordae technique) and leaflet resection (Resection technique). However, there is still a debate in the literature about which is the optimal one. In this context, we performed an image-based computational fluid dynamic study to evaluate blood dynamics in the two surgical techniques.MethodsWe considered a healthy subject (H) and two patients (N and R) who underwent surgery for the prolapse of the posterior leaflet and were operated with the Neochordae and Resection technique, respectively. Computational Fluid Dynamics (CFD) was employed with prescribed motion of the entire left heart coming from cine-MRI images, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method for managing valve dynamics. We created three different virtual scenarios where the operated mitral valves were inserted in the same left heart geometry of the healthy subject to study the differences attributed only to the two techniques.ResultsWe compared the three scenarios by quantitatively analyzing ventricular velocity patterns and pressures, transition to turbulence, and the ventricle ability to prevent thrombi formation. From these results we found that both the operated cases were able to restore almost physiological blood dynamic conditions, with some differences due to the reduced mobility of the Resection posterior leaflet. Conclusions: Our findings suggest that the Neochordae technique developed a slightly more physiological flow with respect to the Resection technique. The latter gave rise to a different direction of the mitral jet during diastole increasing the turbulence that is associated with ventricular effort and hemolysis, with also a larger ability to washout the ventricular apex preventing from thrombi formation.
Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decreases ISR activation in DRG neurons
Authors: Yousuf Muhammad Saad , Mancilla Moreno Marisol , Li Jiahe , He Lucy , Royer Danielle , Zhang Jennifer , Woodall Brodie J , Grace Peter M , Price Theodore J 
Published: December 2023

AbstractDiabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes mechanical hypersensitivity in mice by inducing the integrated stress response (ISR), which is characterized by phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of antioxidant proteins that neutralize MGO. We hypothesized that activating Nrf2 using diroximel fumarate (DRF) would alleviate MGO-induced pain hypersensitivity. We pretreated male and female C57BL/6 mice daily with oral DRF prior to intraplantar injection of MGO (20 ng). DRF (100 mg/kg) treated animals were protected from developing MGO-induced mechanical and cold hypersensitivity. UsingNrf2knockout mice we demonstrate that Nrf2 is necessary for the anti-nociceptive effects of DRF. In cultured mouse and human dorsal root ganglion (DRG) sensory neurons, we found that MGO induced elevated levels of p-eIF2α. Co-treatment of MGO (1 µM) with monomethyl fumarate (MMF, 10, 20, 50 µM), the active metabolite of DRF, reduced p-eIF2α levels and prevented aberrant neurite outgrowth in human DRG neurons. Our data show that targeting the Nrf2 antioxidant system with DRF is a strategy to potentially alleviate pain associated with elevated MGO levels.PerspectiveThis study demonstrates that activating Nrf2 with DRF prevents the development of pain caused by MGO in mice and reduces ISR in mouse and human DRGin vitromodels. We propose that Nrf2 activators like DRF should be tested to alleviate diabetic neuropathic pain associated with elevated MGO in patients.Graphical AbstractArticle HighlightsMGO induces mechanical and cold hypersensitivity in mice that is prevented with pre-treatment with DRF.DRF pre-treatment does not protect Nrf2-knockout mice from developing pain hypersensitivity suggesting that Nrf2 is necessary for DRF’s antinociceptive effects.MMF, the active metabolite of DRF, prevents MGO-induced increase in p-eIF2a levels in mouse and human DRG neuronsin vitro.MMF prevents MGO-induced aberrant neurite outgrowth in human DRG neurons.Nrf2 activators, like the FDA-approved DRF, is an option to alleviate neuropathic pain in patients with diabetes.
Online stimulation of prefrontal cortex during practice increases motor variability and modulates later cognitive transfer: a randomized, double-blinded & sham-controlled tDCS study
Authors: Prabhu Nisha Maria , Lehmann Nico , Kaminski Elisabeth , Müller Notger , Taubert Marco 
Published: December 2023

AbstractBackgroundThe benefits of learning a motor skill extend to improved task-specific cognitive abilities. The mechanistic underpinnings of this motor-cognition relationship potentially rely on overlapping neural resources involved in both processes, an assumption lacking causal evidence.ObjectivesWe hypothesize that interfering with prefrontal networks would affect concurrent motor skill performance, long-term learning and associated cognitive functions dependent on similar networks (transfer).MethodsWe conducted a randomized, double-blinded, sham-controlled brain stimulation study using transcranial direct current stimulation (tDCS) in young adults spanning over three weeks to assess the role of the prefrontal regions in learning a complex balance task and long-term cognitive performance.ResultsBalance training combined with active tDCS led to higher performance variability in the trained task as compared to the sham group, without affecting the learning rate. Furthermore, active tDCS also positively impacted performance in untrained motor and cognitive tasks.ConclusionThe findings of this study help ascertaining the networks directly involved in learning a complex motor task and its implications on cognitive function. Hence, opening up the possibility of harnessing the observed frontal networks involved in resource mobilization in instances of aging, brain lesion/injury or dysfunction.
HyLight: Strain aware assembly of low coverage metagenomes
Authors: Kang Xiongbin , Zhang Wenhai , Luo Xiao , Schönhuth Alexander 
Published: December 2023

AbstractDifferent strains of identical species can vary substantially in terms of their spectrum of biomedically relevant phenotypes. Reconstructing the genomes of a microbial community at strain level poses major methodical challenges, because relative frequencies of individual strains match the rate of sequencing errors, which hampers the identification of their characteristic genetic variants. While next-generation sequencing (NGS) reads are too short to span complex repetitive regions, the considerably longer third-generation sequencing (TGS) reads are affected by larger sequencing error rates or are just significantly more expensive. Suppressing TGS coverage to limit costs implies losses in terms of the accuracy of the assemblies. Therefore, existing approaches have remained fragmentary: all approaches presented so far agree on losses in strain awareness, accuracy, possibly excessive costs of the assemblies, or combinations thereof.We present HyLight as, to the best of our knowledge, the first metagenome assembly approach that is not affected by any of the aforementioned drawbacks. In experiments, we demonstrate that HyLight assemblies are strain-aware, contiguous, contain little errors, and because operating on low coverage TGS data of the cheap kind, come at drastically reduced costs. HyLight implements hybrid assembly, which exploits the complementarity of TGS and NGS data. For unifying the two types of data, HyLight utilizes strain resolved overlap graphs (OG), which support the accurate reconstruction of the individual members of microbial communities at strain level: HyLight outperforms existing approaches in terms of strain identity preserving sequence by on average 25.53% (across all experiments / data sets: first quartile: 21.53%, median: 26.81%, third quartile: 31.98%), achieving near-complete strain awareness on many data sets. In summary, HyLight appears to implement the first protocol that delivers assemblies that are strain-aware, contiguous and accurate in combination.
Perceptual Foundation and Extension to Phase Tagging for Rapid Invisible Frequency Tagging (RIFT)
Authors: Spaak Eelke , Bouwkamp Floortje G. , de Lange Floris P. 
Published: December 2023

AbstractRecent years have seen the emergence of a visual stimulation protocol called Rapid Invisible Frequency Tagging (RIFT) in cognitive neuroscience. In RIFT experiments, visual stimuli are presented at a rapidly and sinusoidally oscillating luminance, using high refresh rate projection equipment. Such stimuli result in strong steady-state responses in visual cortex, measurable extracranially using EEG or MEG. The high signal-to-noise ratio of these neural signals, combined with the alleged invisibility of the manipulation, make RIFT a potentially promising technique to study the neural basis of visual processing. In this study, we set out to resolve two fundamental, yet still outstanding, issues regarding RIFT; as well as to open up a new avenue for taking RIFT beyond frequency tagging per se. First, we provide robust evidence that RIFT is indeed subjectively undetectable, going beyond previous anecdotal reports. Second, we demonstrate that full-amplitude luminance or contrast manipulation offer the best tagging results. Third and finally, we demonstrate that, in addition to frequency tagging, phase tagging can reliably be used in RIFT studies, opening up new avenues for constructing RIFT experiments. Together, this provides a solid foundation for using RIFT in visual cognitive neuroscience.
Genetic evidence of a hybrid swarm between Alpine ibex and domestic goat
Authors: Brambilla Alice , Zehnder Noel , Bassano Bruno , Rossi Luca , Grossen Christine 
Published: December 2023

AbstractImproving the understanding of the causes and effects of anthropogenic hybridization is fundamental to ensure the conservation of wild species, particularly in the case of hybridization between wild species and their domestic relatives. Knowledge is missing for many species also because of a lack of appropriate tools for hybrid identification. Here, coupling genotype and phenotype analysis, we carried out an extensive investigation of ongoing hybridization in Alpine ibexCapra ibex, a mountain ungulate of conservation concern from a genetic perspective. By genotyping at 63 diagnostic and 465 neutral SNPs 20 suspected hybrids and 126 Alpine ibex without suspicious phenotype, representing eight populations across a major part of the species distribution, we found evidence for ongoing hybridization between Alpine ibex and domestic goat. We identified different levels of hybridization including back crosses into both Alpine ibex and domestic goat. Our results suggest a lack of reproductive barriers between the two species and good survival and reproductive success of the hybrids. Hybridization was locally intense, alike a hybrid swarm, but not spread across the rest of the species distribution. Most of the hybrids were discovered in two locations in the North-West of Italy, while random sampling of individuals from different areas did not provide evidence of recent hybridization. Our method, based on Amplicon sequencing of 63 diagnostic SNPs specifically developed for this purpose, allowed us to identify hybrids and back crosses up to the 4th-5thgeneration and was suitable for genetic samples of different quality, although with varying levels of certainty regarding the exact number of generations passed since hybridization. Based on the paired analysis of genotype and phenotype we provide guidelines for a first identification of hybrids in the field and suggest a procedure for the reliable identification of hybrids.