bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic basis of lineage-specific evolution of fruit traits in hexaploid persimmon
Authors: Horiuchi Ayano , Masuda Kanae , Shirasawa Kenta , Onoue Noriyuki , Matsuzaki Ryusuke , Tao Ryutaro , Kubo Yasutaka , Ushijima Koichiro , Akagi Takashi 
Published: May 2023

AbstractFrequent polyploidization events in plants have led to the establishment of many lineage-specific traits representing each species. Little is known about the genetic bases for these specific traits in polyploids, presumably due to plant genomic complexity and their difficulties of applying genetic approaches. Hexaploid Oriental persimmon (Diospyros kaki) has evolved specific fruit characters, including wide variations in fruit shapes and astringency. In this study, using whole-genome diploidized/quantitative genotypes from ddRAD-Seq data of 173 persimmon cultivars, we examined their population structures and potential correlations between their structural transitions and variations in nine fruit traits. The population structures of persimmon cultivars were highly randomized and not substantially correlated with the representative fruit traits focused on in this study, except for fruit astringency. With genome-wide association analytic tools considering polyploid alleles, we identified the loci associated with the nine fruit traits; we mainly focused on fruit-shape variations, which have been numerically characterized by principal component analysis of elliptic Fourier descriptors. The genomic regions that putatively underwent selective sweep exhibited no overlap with the loci associated with these persimmon-specific fruit traits. These insights will contribute to understanding of the genetic mechanisms by which fruit traits are independently established, possibly due to polyploidization events.
The Haplotype-resolved Autotetraploid Genome Assembly Provides Insights into the genomic evolution and fruit divergence in Wax apple (Syzygium samarangense(BI.) Merr.et Perry)
Authors: Wei Xiuqing , Chen Min , Zhang Xijuan , Wang Yinghao , Li Liang , Xu Ling , Wang Huanhuan , Jiang Mengwei , Wang Caihui , Zeng Lihui , Xu Jiahui 
Published: May 2023

AbstractThe wax apple (Syzygium samarangense) is an economically important fruit crop with great potential value to human health because it has rich antioxidant substances. Here, we presented one haplotype-resolved autotetraploid genome assembly of the wax apple with size of 1.59 Gb. Comparative genomic analysis revealed three rounds of whole-genome duplication (WGD) events, including two independent WGDs after WGT-γ. Resequencing analysis of 35 accessions partitioned these individuals into two distinct groups, including 28 landraces and seven cultivated species, and several selectively swept genes possibly contributed to fruit growth, includingKRP1-like, IAA17-like, GME-like, andFLACCA-likegenes. Transcriptome analysis in three different varieties during flower and fruit development identified key genes related to fruit size, sugar content, and male sterility. We foundAP2also affects the fruit size by regulating the sepal development in wax apples. The expression of sugar transport-related genes (SWEETs andSUTs) was high in ‘ZY’, likely contributing to a high level of sugar content. Male sterility in ‘Tub’ was associated with tapetal abnormalities due to the decreased expression ofDYT1, TDF1, andAMS, which affects the early tapetum development. The chromosome-scale genome and large-scale transcriptome data presented in this study offer new valuable resources for biological research onS. samarangense, and sheds new light on fruit size control, sugar metabolism, and male sterility regulatory metabolism in wax apple.
RNA structures and dynamics with Å resolution revealed by x-ray free electron lasers
Authors: Zielinski Kara A. , Sui Shuo , Pabit Suzette A. , Rivera Daniel A. , Wang Tong , Hu Qingyue , Kashipathy Maithri M. , Lisova Stella , Schaffer Chris B. , Mariani Valerio , Hunter Mark S. , Kupitz Christopher , Moss Frank R. , Poitevin Frédéric P. , Grant Thomas D. , Pollack Lois 
Published: May 2023

AbstractRNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free electron laser sources to reveal the formation and ready identification of Å scale features in structured and unstructured RNAs. New structural signatures of RNA secondary and tertiary structures are identified through wide angle solution scattering experiments. With millisecond time resolution, we observe an RNA fold from a dynamically varying single strand through a base paired intermediate to assume a triple helix conformation. While the backbone orchestrates the folding, the final structure is locked in by base stacking. In addition to understanding how RNA triplexes form and thereby function as dynamic signaling elements, this new method can vastly increase the rate of structure determination for these biologically essential, but mostly uncharacterized macromolecules.
Characterizing glucokinase variant mechanisms using a multiplexed abundance assay
Authors: Gersing Sarah , Schulze Thea K. , Cagiada Matteo , Stein Amelie , Roth Frederick P. , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus 
Published: May 2023

AbstractAmino acid substitutions can perturb protein activity in multiple ways. Understanding their mechanistic basis may pinpoint how residues contribute to protein function. Here, we characterize the mechanisms of human glucokinase (GCK) variants, building on our previous comprehensive study on GCK variant activity. We assayed the abundance of 95% of GCK missense and nonsense variants, and found that 43% of hypoactive variants have a decreased cellular abundance. By combining our abundance scores with predictions of protein thermodynamic stability, we identify residues important for GCK metabolic stability and conformational dynamics. These residues could be targeted to modulate GCK activity, and thereby affect glucose homeostasis.
Identification of the intracellular protein targets of a bio-active clickable half-sandwich iridium complex by chemical proteomics
Authors: Ramos Robin , Karaiskou Anthi , Botuha Candice , Trichet Michaël , Dingli Florent , Forté Jérémy , Lam France , Canette Alexis , Chaumeton Chloé , Salome Murielle , Chenuel Thomas , Bergonzi Céline , Meyer Philippe , Bohic Sylvain , Loew Damarys , Salmain Michèle , Sobczak-Thépot Joëlle 
Published: May 2023

AbstractIdentification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C^N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high affinity targets. Upon iridium complex treatment, HSP90 folding activity was inhibitedin vitroand major cytoskeleton disorganization was observed. We used a wide array of imaging and biochemical methods to validate selected targets and obtain a multiscale overview of the effects of this complex on live human cells. We demonstrate that it behaves as a dual agent, inducing both electrophilic and oxidative stresses in cells that account for its cytotoxicity.
Annihilation of action potentials induces electrical coupling between neurons
Authors: Schlötter Moritz , Maret Georg , Kleineidam Christoph J. 
Published: May 2023

AbstractNeurons generate and propagate electrical pulses called action potentials which annihilate on arrival at the axon terminal. We measure the extracellular electric field generated by propagating and annihilating action potentials and find that on annihilation, action potentials expel a local discharge. The discharge at the axon terminal generates an inhomogeneous electric field that immediately influences target neurons and thus provokes ephaptic coupling. Our measurements are quantitatively verified by a powerful analytical model which reveals excitation and inhibition in target neurons, depending on position and morphology of the source-target arrangement. Our model is in full agreement with experimental findings on ephaptic coupling at the well-studied Basket cell - Purkinje cell synapse. It is able to predict ephaptic coupling for any other synaptic geometry as illustrated by a few examples.
Pro-social and pro-cognitive effects of LIT-001, a novel oxytocin receptor agonist in a neurodevelopmental model of schizophrenia
Authors: Piotrowska Diana , Potasiewicz Agnieszka , Popik Piotr , Nikiforuk Agnieszka 
Published: May 2023

ABSTRACTSocial and cognitive dysfunctions are the most persistent symptoms of schizophrenia. Since oxytocin (OXT) is known to play a role in social functions and modulates cognitive processes, we investigated the effects of a novel, nonpeptide, selective OXT receptor agonist, LIT-001, in a neurodevelopmental model of schizophrenia. Administration of methylazoxymethanol acetate (MAM; 22 mg/kg) on the 17thday of pregnancy is known to cause developmental disturbances of the brain, which lead to schizophrenia-like symptomatology in the offspring. Here, we examined the effects of acutely administered LIT-001 (1, 3, and 10 mg/kg) in MAM-exposed males and females on social behaviour, communication and cognition.We report that MAM-treated adult male and female rats displayed reduced social behaviour, ultrasonic communication and novel object recognition test performance. LIT-001 partially reversed these deficits, increasing the total social interaction time and the number of ‘happy’ 50 kHz ultrasonic calls in male rats. The compound ameliorated MAM-induced deficits in object discrimination in both sexes.Present results confirm the pro-social activity of LIT-001 and demonstrate its pro-cognitive effects following acute administration.
Lateralized Sensorimotor Evoked Potentials during Visuomotor Transformation in Real and Imagined Movements
Authors: Syrov Nikolay , Yakovlev Lev , Kaplan Alexander , Lebedev Mikhail 
Published: May 2023

ABSTRACTThe neural mechanisms underlying motor preparation have attracted much attention, particularly because of the assertion that they are similar to the mechanisms of motor imagery (MI), a technique widely used in motor rehabilitation and brain-computer interfaces (BCIs). Here we clarified the process of visuomotor transformation for the real and imagined movements by analyzing EEG responses that were time locked to the appearance of visual targets and movement onsets. The experimental task required responding to target stimuli with button presses or imagined button presses while ignoring distractors. We examined how different components of movement-related potentials (MRPs) varied depending on the reaction time (RT) and interpreted the findings in terms of the motor noise accumulation hypothesis. Furthermore, we compared MRPs and event-related desynchronization (ERD) for overt motor actions versus motor imagery. For the MRPs, we distinguished lateralized readiness potentials (LRPs) and reafferent potentials (RAPs). While MRPs were similar for the real and imagined movements, imagery-related potentials were not lateralized. The amplitude of the late potentials that developed during motor imagery at the same time RAPs occurred during real movements was correlated with the amplitude of β-ERD. As such they could have represented sensorimotor activation triggered by the imagery. LRPs that occurred during real movements lasted longer for longer RTs, which is consistent with activity accumulation in the motor cortex prior to overt action onset. LRPs occurred for non-target stimuli, as well, but they were small and short lived. We interpret these results in terms of a visuomotor transformation, where information flows from visual to motor areas and results in a movement, a decision not to move and/or a mental image of a movement. The amplitude of the late positive peak that developed during MI was correlated with the amplitude of the β-ERD. Since the latency of this component was consistent with the timing of RAP, we suggest that it is a non-lateralized RAP-like component associated with sensorimotor activation during kinesthetic MI.
Dual-system free-operant avoidance: extension of a theory
Authors: Perez Omar D. , Dickinson Anthony 
Published: May 2023

AbstractOur theory of positively reinforced free-operant behavior (Perez & Dickinson, 2020) assumes that responding is controlled by 2 systems. One system is sensitive to the correlation between response and reinforcement rates and controls goal-directed behavior, whereas a habitual system learns by reward prediction error. We present an extension of this theory to the aversive domain that explains why free-operant avoidance responding increases with both the experienced rate of negative reinforcement and the difference between this rate and that programmed by the avoidance schedule. The theory also assumes that the habitual component is reinforced by the acquisition of aversive inhibitory properties by the feedback stimuli generated by responding, which then act as safety signals that reinforce habit performance. Our analysis suggests that the distinction between habitual and goal-directed control of rewarded behavior can also be applied to the aversive domain.
Hierarchical Modelling of Crossing Fibres in the White Matter
Authors: Rafipoor Hossein , Lange Frederik J. , Arthofer Christoph , Cottaar Michiel , Jbabdi Saad 
Published: May 2023

ABSTRACTWhile diffusion MRI is typically used to estimate microstructural properties of tissue in volumetric elements (voxels), more specificity can be obtained by separately modelling the properties of individual fibre populations within a voxel. In the context of cross-subjects modelling, these so-called fixel-based analyses require identifying equivalent fibre populations. This is usually done post-hoc, after estimating fibre orientations for individual subjects independently and subsequently matching the fixels between subjects. This approach can fail due to individual differences in fibre orientation distributions.Here, we introduce a hierarchical framework for fitting crossing fibre models to diffusion MRI data in a population of subjects. This hierarchical setup guarantees that the crossing fibres are consistent by construction and, therefore, comparable across subjects. We propose an expectation-maximisation approach to fit the model, which can scale to large numbers of subjects. This approach produces a crossing-fibre white matter fibre template, which can be used to estimate fibre-specific parameters that are consistent across subjects and, hence, can be used in fixel-based statistical analyses.
Dissociative effects of age on neural differentiation at the category and item level
Authors: Srokova Sabina , Aktas Ayse N. Z. , Koen Joshua D. , Rugg Michael D. 
Published: May 2023

AbstractIncreasing age is associated with age-related neural dedifferentiation, a reduction in the selectivity of neural representations which has been proposed to contribute to cognitive decline in older age. Recent findings indicate that when operationalized in terms of selectivity for different perceptual categories, age-related neural dedifferentiation, and the apparent age-invariant association of neural selectivity with cognitive performance, are largely restricted to the cortical regions typically recruited during scene processing. It is currently unknown whether this category-level dissociation extends to metrics of neural selectivity defined at the level of individual stimulus items. Here, we examined neural selectivity at the category and item levels using multivoxel pattern similarity analysis (PSA) of fMRI data. Healthy young and older male and female adults viewed images of objects and scenes. Some items were presented singly, while others were either repeated or followed by a ‘similar lure’. Consistent with recent findings, category-level PSA revealed robustly lower differentiation in older than younger adults in scene-selective, but not object-selective, cortical regions. By contrast, at the item level, robust age-related declines in neural differentiation were evident for both stimulus categories. Moreover, we identified an age-invariant association between category-level scene-selectivity in the parahippocampal place area and subsequent memory performance, but no such association was evident for item-level metrics. Lastly, category and item-level neural metrics were uncorrelated. Thus, the present findings suggest that age-related category- and item-level dedifferentiation depend on distinct neural mechanisms.Significance StatementCognitive aging is associated with a decline in the selectivity of the neural responses within cortical regions that respond differentially to distinct perceptual categories (age-related neural dedifferentiation). However, prior research indicates that while scene-related selectivity is reduced in older age and is correlated with cognitive performance independently of age, selectivity for object stimuli is typically not moderated by age or memory performance. Here, we demonstrate that neural dedifferentiation is evident for both scene and object exemplars when it is defined in terms of the specificity of neural representations at the level of individual exemplars. These findings suggest that neural selectivity metrics for stimulus categories and for individual stimulus items depend on different neural mechanisms.
Endogenous recapitulation of Alzheimer’s disease neuropathology through human 3D direct neuronal reprogramming
Authors: Sun Zhao , Kwon Ji-Sun , Ren Yudong , Chen Shawei , Cates Kitra , Lu Xinguo , Walker Courtney K. , Karahan Hande , Sviben Sanja , Fitzpatrick James A J , Valdez Clarissa , Houlden Henry , Karch Celeste M. , Bateman Randall J. , Sato Chihiro , Mennerick Steven J. , Diamond Marc I. , Kim Jungsu , Tanzi Rudolph E. , Holtzman David M. , Yoo Andrew S. 
Published: May 2023

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder that primarily affects elderly individuals, and is characterized by hallmark neuronal pathologies including extracellular amyloid-β (Aβ) plaque deposition, intracellular tau tangles, and neuronal death. However, recapitulating these age-associated neuronal pathologies in patient-derived neurons has remained a significant challenge, especially for late-onset AD (LOAD), the most common form of the disorder. Here, we applied the high efficiency microRNA-mediated direct neuronal reprogramming of fibroblasts from AD patients to generate cortical neurons in three-dimensional (3D) Matrigel and self-assembled neuronal spheroids. Our findings indicate that neurons and spheroids reprogrammed from both autosomal dominant AD (ADAD) and LOAD patients exhibited AD-like phenotypes linked to neurons, including extracellular Aβ deposition, dystrophic neurites with hyperphosphorylated, K63-ubiquitin-positive, seed-competent tau, and spontaneous neuronal death in culture. Moreover, treatment with β- or γ-secretase inhibitors in LOAD patient-derived neurons and spheroids before Aβ deposit formation significantly lowered Aβ deposition, as well as tauopathy and neurodegeneration. However, the same treatment after the cells already formed Aβ deposits only had a mild effect. Additionally, inhibiting the synthesis of age-associated retrotransposable elements (RTEs) by treating LOAD neurons and spheroids with the reverse transcriptase inhibitor, lamivudine, alleviated AD neuropathology. Overall, our results demonstrate that direct neuronal reprogramming of AD patient fibroblasts in a 3D environment can capture age-related neuropathology and reflect the interplay between Aβ accumulation, tau dysregulation, and neuronal death. Moreover, miRNA-based 3D neuronal conversion provides a human-relevant AD model that can be used to identify compounds that can potentially ameliorate AD-associated pathologies and neurodegeneration.
Computationally efficient demographic history inference from allele frequencies with supervised machine learning
Authors: Tran Linh N. , Sun Connie K. , Struck Travis J. , Sajan Mathews , Gutenkunst Ryan N. 
Published: May 2023

AbstractInferring past demographic history of natural populations from genomic data is of central concern in many studies across research fields. Previously, our group had developed dadi, a widely used demographic history inference method based on the allele frequency spectrum (AFS) and maximum composite likelihood optimization. However, dadi’s optimization procedure can be computationally expensive. Here, we developed donni (demography optimization via neural network inference), a new inference method based on dadi that is more efficient while maintaining comparable inference accuracy. For each dadi-supported demographic model, donni simulates the expected AFS for a range of model parameters then trains a set of Mean Variance Estimation neural networks using the simulated AFS. Trained networks can then be used to instantaneously infer the model parameters from future input data AFS. We demonstrated that for many demographic models, donni can infer some parameters, such as population size changes, very well and other parameters, such as migration rates and times of demographic events, fairly well. Importantly, donni provides both parameter and confidence interval estimates from input AFS with accuracy comparable to parameters inferred by dadi’s likelihood optimization while bypassing its long and computationally intensive evaluation process. donni’s performance demonstrates that supervised machine learning algorithms may be a promising avenue for developing more sustainable and computationally efficient demographic history inference methods.
Validation of hypermethylated DNA regions found in colorectal cancers as potential aging-independent biomarkers of precancerous colorectal lesions
Authors: Sajibu Sija , Sonder Emanuel , Tiwari Amit , Orjuela Stephany , Parker Hannah R. , The Frans Olivier , Gubler Christoph , Marra Giancarlo , Robinson Mark D. 
Published: May 2023

AbstractBackgroundWe previously identified 16,772 colorectal cancer-associated hypermethylated DNA regions that were also detectable in precancerous colorectal lesions (preCRCs) and unrelated to normal mucosal aging. We have now conducted a study to validate 990 of these differentially methylated DNA regions (DMR) in a new series of preCRCs.MethodsWe used targeted bisulfite sequencing to validate these 990 potential biomarkers in 59 preCRC tissue samples (41 conventional adenomas, 18 sessile serrated lesions), each with a patient-matched normal mucosal sample. Based on differential DNA methylation tests, a panel of (candidate) DMRs was chosen on a subset of the (our) cohort and validated on the remaining part of our cohort and (two) further publicly available datasets with respect to their stratifying potential between preCRCs and normal mucosa.ResultsStrong statistical significance for the difference in methylation levels was observed across the full set of 990 investigated DMRs. From these, a selected candidate panel of 30 DMRs correctly identified 58/59 tumors (area under the receiver operating curve: 0.998).ConclusionsThese validated DNA hypermethylation markers can be exploited to develop more accurate noninvasive colorectal tumor screening assays.