bluuebunny/crossref_metadata_2025_split huggingface dataset:
ortho_seqs: A Python tool for sequence analysis and higher order sequence–phenotype mapping
Authors: Nafees Saba , Pranathi Vemuri Venkata Naga , Woollacott Miles , Solak Ahmet Can , Logan Phoenix , McGeever Aaron , Yoo Olivia , Rice Sean H. 
Published: September 2022

AbstractMotivationAn important goal in sequence analysis is to understand how parts of DNA, RNA, or protein sequences interact with each other and to predict how these interactions result in given phenotypes. Mapping phenotypes onto underlying sequence space at first- and higher order levels in order to independently quantify the impact of given nucleotides or residues along a sequence is critical to understanding sequence–phenotype relationships.ResultsWe developed a Python software tool, ortho_seqs, that quantifies higher order sequence-phenotype interactions based on our previously published method of applying multivariate tensor-based orthogonal polynomials to biological sequences. Using this method, nucleotide or amino acid sequence information is converted to vectors, which are then used to build and compute the first- and higher order tensor-based orthogonal polynomials. We derived a more complete version of the mathematical method that includes projections that not only quantify effects of given nucleotides at a particular site, but also identify the effects of nucleotide substitutions. We show proof of concept of this method, provide a use case example as applied to synthetic antibody sequences, and demonstrate the application of ortho_seqs to other other sequence–phenotype datasets.Availabilityhttps://github.com/snafees/ortho_seqs & documentation https://ortho-seqs.readthedocs.io/
Neuroprotective tissue adaptation induced by IL-12 attenuates CNS inflammation
Authors: Andreadou Myrto , Ingelfinger Florian , De Feo Donatella , Friebel Ekaterina , Tuzlak Selma , Cramer Teresa M.L. , Schreiner Bettina , Eede Pascale , Schneeberger Shirin , Geesdorf Maria , Ridder Frederike , Welsh Christina , Kirschenbaum Daniel , Tyagarajan Shiva K. , Greter Melanie , Heppner Frank L. , Mundt Sarah , Becher Burkhard 
Published: September 2022

AbstractIL-12 is a well-established driver of type 1 immune responses. Paradoxically, in several autoimmune conditions including neuroinflammation, IL-12 reduces pathology and exhibits regulatory properties. Yet, the mechanism and the involved cellular players behind this immune regulation remain elusive. To identify the IL-12-responsive elements which prevent immunopathology, we generated mouse models lacking a functional IL-12 receptor either in all cells or in specific populations within the immune or central nervous system (CNS) compartments, and induced experimental autoimmune encephalomyelitis (EAE), which models human Multiple Sclerosis (MS). This revealed that the CNS tissue-protective features of IL-12 are mediated by cells of the neuroectoderm, and not immune cells. Importantly, sections of brain from patients with MS show comparable patterns of expression, indicating parallel mechanisms in humans. By combining spectral flow cytometry, bulk and single-nucleus RNA sequencing, we uncovered an IL-12-induced neuroprotective adaption of the neuroectoderm critically involved in maintaining CNS tissue integrity during inflammation.
Unique potential of immature adult-born neurons for the remodeling of CA3 spatial maps
Authors: Mugnaini Matías , Trinchero Mariela F. , Schinder Alejandro F. , Piatti Verónica C. , Kropff Emilio 
Published: September 2022

ABSTRACTMammalian hippocampal circuits undergo extensive remodeling through adult neurogenesis. While this process has been widely studied, the specific contribution of adult-born granule cells (aGCs) to spatial operations in the hippocampus remains unknown. Here we show that optogenetic activation of 4-week-old (young) aGCs in free-foraging mice produces a non- reversible reconfiguration of spatial maps in proximal CA3, while rarely evoking neural activity. Stimulation of the same neuronal cohort on subsequent days recruits CA3 neurons with increased efficacy but fails to induce further remapping. In contrast, stimulation of 8- week-old (mature) aGCs can reliably activate CA3 cells but produce no alterations in spatial maps. Our results reveal a unique role of young aGCs in remodeling CA3 representations, a potential that can be depleted and is lost with maturation. This ability could contribute to generate orthogonalized downstream codes supporting pattern separation.
Non-invasive temporal interference electrical stimulation of the human hippocampus
Authors: Violante Ines R. , Alania Ketevan , Cassarà Antonino M. , Neufeld Esra , Acerbo Emma , Carron Romain , Williamson Adam , Kurtin Danielle L. , Rhodes Edward , Hampshire Adam , Kuster Niels , Boyden Edward S. , Pascual-Leone Alvaro , Grossman Nir 
Published: September 2022

ABSTRACTDeep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders however its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modelling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging (fMRI) and behaviour experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.
Parafoveal and foveal N400 effects in natural reading: A timeline of semantic processing from fixation-related potentials
Authors: Li Nan , Wang Suiping , Kornrumpf Florian , Sommer Werner , Dimigen Olaf 
Published: September 2022

ABSTRACTThe depth at which parafoveal words are processed during reading is an ongoing topic of debate. Recent studies using RSVP-with-flanker paradigms have shown that implausible words within sentences elicit N400 components while they are still in parafoveal vision, suggesting that the semantics of parafoveal words can be accessed to rapidly update the sentence representation. To study this effect in natural reading, we combined the co-registration of eye movements and EEG with the deconvolution modeling of fixation-related potentials (FRPs) to test whether semantic plausibility is processed parafoveally during Chinese sentence reading. For one target word per sentence, both its parafoveal and foveal plausibility were orthogonally manipulated using the boundary paradigm. Consistent with previous eye movement studies, we observed a delayed effect of parafoveal plausibility on fixation durations that only emerged on the foveal word. Crucially, in FRPs aligned to the pre-target fixation, a clear N400 effect emerged already based on parafoveal plausibility, with more negative voltages for implausible previews. Once participants fixated the target, we again observed an N400 effect of foveal plausibility. Interestingly, this foveal N400 was absent whenever the preview had been implausible, indicating that when a word’s (im)plausibility is already processed in parafoveal vision, this information is not revised anymore upon direct fixation. Implausible words also elicited a late positive complex (LPC), but exclusively in foveal vision. Our results provide convergent neural and behavioral evidence for the parafoveal uptake of semantic information, but also indicate different contributions of parafoveal versus foveal information towards higher-level sentence processing.
Combining historical agricultural and climate datasets sheds new light on early 20thcentury barley performance
Authors: Raymond Joanna , Mackay Ian , Penfield Steven , Lovett Andrew , Philpott Haidee , Dorling Stephen 
Published: September 2022

AbstractBarley (Hordeum vulgare ssp. vulgare) is cultivated globally across a wide range of environments, both in highly productive agricultural systems and in subsistence agriculture and provides valuable feedstock for the animal feed and malting industries. However, as the climate changes there is an urgent need to identify adapted spring barley varieties that will consistently yield highly under increased environmental stresses. In this research we combined recently released historical weather data with published early 20thcentury Irish spring barley trials data for two heritage varieties:ArcherandGoldthorpe, following an analysis first published by Student in 1923. Using linear mixed models, we show that interannual variation in observed spring barley yields can be partially explained by recorded weather variability. We find that whilstArcherlargely yields more highly,Goldthorpeis more stable under wetter growing conditions, highlighting the importance of considering growing climate in variety selection. Furthermore, this study demonstrates the benefits of access to historical trials and climatic data and the importance of incorporating climate data in modern day breeding programmes to improve climate resilience of future varieties.
Determinants of survival and dispersal along the range expansion of a biological invasion
Authors: Edeline Eric , Starck Agnès , Bennevault Yoann , Paillisson Jean-Marc , Petit Eric J. 
Published: September 2022

ABSTRACTProjecting and managing the future response of biological systems to global change requires a mechanistic understanding of how climate and ecology jointly drive species demography and range dynamics. Such knowledge is particularly crucial when it comes to invasive species, which expansion may have far-reaching consequences for recipient ecosystems. Here, we use mark recapture in replicated outdoor mesocosms to examine how survival and dispersal, two key drivers of population and range dynamics, respond to climate and ecology in the invasive red swamp crayfish (Procambarus clarkii) along an invasion gradient. We show that crayfish survival probability increased with (i) increasing body size at high (but not low) crayfish density and (ii) with warmer temperatures, and decreased (i) with increasing body condition and (ii) under higher crayfish density. Overland dispersal probability by crayfish increased with increasing (i) body-size, (ii) body condition and (iii) temperatures. In contrast, crayfish from range-edge and range-core habitats had similar survival and overland dispersal probabilities, suggesting no evolution of the crayfish expansion potential along the invasion gradient. Our results highlight that species population dynamics and range shifts in a changing world are driven by joint contributions from both climate and ecology. InP. clarkii, global warming will simultaneously promote both a demographic increase and a geographic range expansion, especially in populations dominated by large-bodied individuals. In already-invaded ecosystems, selective harvesting of large-bodied crayfish can potentially reduce the dispersal potential of populations and, after a few generations, might further induce an evolutionary decline in fitness traits that is desirable from a management perspective.Open research statementUpon acceptance of this manuscript, data and codes will be made publicly available online on the INRAE data repository (https://entrepot.recherche.data.gouv.fr/dataverse/inrae).
Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis
Authors: Phelps Wesley A. , Hurton Matthew D. , Ayers Taylor N. , Carlson Anne E. , Rosenbaum Joel C. , Lee Miler T. 
Published: September 2022

AbstractAfter fertilization, maternally contributed factors to the egg initiate the transition to pluripotency to give rise to embryonic stem cells, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that pervasive regulatory remodeling has shaped the earliest stages of development. Here, we show that maternal homologs of mammalian pluripotency reprogramming factors OCT4 and SOX2 divergently activate the two subgenomes of Xenopus laevis, an allotetraploid that arose from hybridization of two diploid species ~18 million years ago. Although most genes have been retained as two homeologous copies, we find that a majority of them undergo asymmetric activation in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in enhancer architecture between the subgenomes, which likely arose through genomic disruptions as a consequence of allotetraploidy. However, comparison with diploid X. tropicalis and zebrafish shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the core vertebrate pluripotency transcriptional program, amid genomic instability following hybridization.
An island “endemic” born out of hybridization between introduced lineages
Authors: Salter Jessie F. , Brumfield Robb T. , Faircloth Brant C. 
Published: September 2022

AbstractHumans have profoundly impacted the distribution of plant and animal species over thousands of years. The most direct example of these effects is human-mediated movement of individuals, either through translocation of individuals within their range or the introduction of species to new habitats. While human involvement may be suspected in species with obvious range disjunctions, it can be difficult to detect natural versus human-mediated dispersal events for populations at the edge of a species’ range, and this uncertainty muddles how we understand the evolutionary history of populations and broad biogeographic patterns. Studies combining genetic data with archeological, linguistic, and historical evidence have confirmed prehistoric examples of human-mediated dispersal; however, it is unclear whether these methods can disentangle recent dispersal events, such as species translocated by European colonizers during the past 500 years. We use genomic DNA from historical specimens and historical records to evaluate three hypotheses regarding the timing and origin of Northern Bobwhites (Colinus virginianus) in Cuba, whose status as an endemic or introduced population has long been debated. We discovered that bobwhites from southern Mexico arrived in Cuba between the 12th and 16th centuries, followed by the subsequent introduction of bobwhites from the southeastern USA to Cuba between the 18th and 20th centuries. These dates suggest the introduction of bobwhites to Cuba was human-mediated and concomitant with Spanish colonial shipping routes between Veracruz, Mexico and Havana, Cuba during this period. Our results identify endemic Cuban bobwhites as a genetically distinct population born of hybridization between divergent, introduced lineages.
All-Aqueous Printing of Viscoelastic Droplets in Yield-Stress Fluids
Authors: Zhu Jinchang , Cai Li-Heng 
Published: September 2022

AbstractAll-aqueous printing of viscoelastic droplets (aaPVD) in yield-stress fluids is the core of an emerging voxelated bioprinting technology that enables the digital assembly of spherical bio-ink particles (DASP) to create functional tissue mimics. However, the mechanism of aaPVD is largely unknown. Here, by quantifying the dynamics of the whole printing process in real-time, we identify two parameters critical to aaPVD: (1) acceleration of print nozzle, and (2) droplet/nozzle diameter ratio. Moreover, we distinguish three stages associated with aaPVD: droplet generation, detachment, and relaxation. To generate a droplet of good roundness, the ink should be a highly viscous shear-thinning fluid. Using particle image velocimetry and scaling theory, we establish a universal description for the droplet displacements at various printing conditions. Along the direction of nozzle movement, the droplet displacement is determined by the detachment number, a dimensionless parameter defined as the ratio between the dragging force from the nozzle and the confinement force from the supporting matrix. Perpendicular to the direction of nozzle movement, the droplet displacement is determined by the Oldroyd number, a dimensionless parameter that describes the yielded area of the supporting matrix near the print nozzle. For a relaxed droplet, the droplet tail length is independent of droplet/nozzle diameter ratio but determined by the nozzle acceleration. We conclude that printing droplets of good fidelity requires a relatively large droplet/nozzle diameter ratio and intermediate nozzle accelerations. These ensure that the droplet is more solid-like to not flow with the nozzle to form a tadpole-like morphology and that the confinement force from the yield-stress fluid is large enough to prevent large droplet displacement. Our results provide the knowledge and tools forin situgenerating and depositing highly viscoelastic droplets of good roundness at prescribed locations in 3D space, which help establish the foundational science for voxelated bioprinting.Statement of SignificanceAnalogues of pixels to two-dimensional (2D) pictures, voxels – in the form of small cubes or spheres – are the basic units of three-dimensional (3D) objects. All-aqueous printing of viscoelastic droplets (aaPVD) is the core of voxelated bioprinting, an emerging technology that uses spherical bio-ink voxels as building blocks to create 3D tissue mimics. By quantifying the dynamics of the whole printing process in real-time, we distinguish the stages associated with aaPVD, identify parameters critical to aaPVD, and develop a universal understanding forin situgenerating and depositing viscoelastic droplets of good roundness at prescribed locations in 3D space. Our results help establish the foundational science for voxelated bioprinting and provide a general approach for precisely manipulating viscoelastic voxels in 3D space.
Perception and Memory Retrieval States are Reflected in Distributed Patterns of Background Functional Connectivity
Authors: Li Y. Peeta , Wang Yida , Turk-Browne Nicholas B. , Kuhl Brice A. , Hutchinson J. Benjamin 
Published: September 2022

ABSTRACTThe same visual input can serve as the target of perception or as a trigger for memory retrieval depending on whether cognitive processing is externally oriented (perception) or internally oriented (memory retrieval). While numerous human neuroimaging studies have characterized how visual stimuli are differentially processed during perception versus memory retrieval, perception and memory retrieval may also be associated with distinct neural states that are independent of stimulus-evoked neural activity. Here, we combined human fMRI with full correlation matrix analysis (FCMA) to reveal potential differences in “background” functional connectivity across perception and memory retrieval states. We found that perception and retrieval states could be discriminated with high accuracy based on patterns of connectivity across (1) the control network, (2) the default mode network (DMN), and (3) retrosplenial cortex (RSC). In particular, clusters in the control network increased connectivity with each other during the perception state, whereas clusters in the DMN were more strongly coupled during the retrieval state. Interestingly, RSC switched its coupling between networks as the cognitive state shifted from retrieval to perception. Finally, we show that background connectivity 1) was fully independent from stimulus-related variance in the signal and, further, 2) captured distinct aspects of cognitive states compared to traditional classification of stimulus-evoked responses. Together, our results reveal that perception and memory retrieval are associated with sustained cognitive states that manifest as distinct patterns of connectivity among large-scale brain networks.
Tactile stimulation restores inhibited stretch reflex attributable to attenuation of la afferents during surprise landing
Authors: Konishi Yu , Yoshii Ryo , Takeshita Daisuke 
Published: September 2022

ABSTRACTPurposeArthrogenic muscle inhibition(AMI) is induced by pathological knee conditions. The present study aimed to investigate the effect of tactile stimulation on reflex changes induced by simulated AMI during unpredictable landing performances.MethodsTwenty participants performed six unilateral landing tasks: 15cm normal landing (15NL), 30cm normal landing(30NL), surprise landing(SL), 30cm normal landing following vibration (30NLV), surprise landing following vibration(SLV), and surprise landing following vibration with Kinesiology-tape(SLK). For the surprise landing tasks, the solid landing platform(15cm) was removed and replaced by a false plate platform. Since the false plate dislodged easily under load, participants unpredictably fell through the plate to the actual landing surface 15cm below. After completing 15NL, 30NL, SL, vibration stimulation was applied to participants’ knees to induce neurological changes similar to AMI. After vibration stimulation, participants performed 30NLV, SLV and SLK in a random order. EMG in the post-landing short latency(31–60 ms) and medium latency(61–90 ms) periods were examined. EMG signals from the vastus lateralis(VL), vastus medialis(VM), and lateral hamstrings(LH) were recorded and compared between tasks.ResultsEMG of all muscles were significantly enhanced in the medium latency period. Enhanced EMG were suppressed by vibration stimulation in the VL, but the suppressed EMG were restored after cutaneous stimulation(p<0.01).ConclusionOur findings suggest that AMI could alter motor control patterns during unpredictable landing, and that tactile stimulation could restore the altered motor control to a normal state. The use of tactile stimulation may help maintain normal motor control patterns in injured individuals.
Rapid and fully automated blood vasculature analysis in 3D light-sheet image volumes of different organs
Authors: Spangenberg Philippa , Hagemann Nina , Squire Anthony , Förster Nils , Krauß Sascha D. , Qi Yachao , Yusuf Ayan Mohamud , Wang Jing , Grüneboom Anika , Kowitz Lennart , Korste Sebastian , Totzeck Matthias , Cibir Zülal , Tuz Ali Ata , Singh Vikramjeet , Siemes Devon , Struensee Laura , Engel Daniel R. , Ludewig Peter , Melo Luiza Martins Nascentes , Helfrich Iris , Chen Jianxu , Gunzer Matthias , Hermann Dirk M. , Mosig Axel 
Published: September 2022

AbstractBlood vasculature represents a complex network of vessels with varying lengths and diameters that are precisely organized in space to allow proper tissue function. Light-sheet fluorescence microscopy (LSFM) is very useful to generate tomograms of tissue vasculature with high spatial accuracy. Yet, quantitative LSFM analysis is still cumbersome and available methods are restricted to single organs and advanced computing hardware. Here, we introduce VesselExpress, an automated software that reliably analyzes six characteristic vascular network parameters including vessel diameter in LSFM data on average computing hardware. VesselExpress is ~100 times faster than other existing vessel analysis tools, requires no user interaction, integrates batch processing, and parallelization. Employing an innovative dual Frangi filter approach we show that obesity induces a large-scale modulation of brain vasculature in mice and that seven other major organs differ strongly in their 3D vascular makeup. Hence, VesselExpress transforms LSFM from an observational to an analytical working tool.