bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hampered AMPK-ULK1 cascade in Alzheimer’s disease (AD) instigates mitochondria dysfunctions and AD-related alterations that are alleviated by metformin
Authors: Mary Arnaud , Barale Samantha , Eysert Fanny , Valverde Audrey , Lacas-Gervais Sandra , Bauer Charlotte , Eddarkaoui Sabiha , Buée Luc , Buée-Scherrer Valérie , Checler Frédéric , Chami Mounia 
Published: December 2024

AbstractBackgroundMitochondrial structure and function alterations are key pathological features in Alzheimer’s disease (AD) brains. The adenosine monophosphate-activated protein kinase (AMPK) and its downstream effector Unc-51 like autophagy activating kinase 1 (ULK1) represent a key node controlling mitochondria health, the alteration of which likely contribute to AD development.MethodsWe designed this study to investigate AMPK-ULK1 activation state in post-mortem human sporadic AD brains, in 3xTgAD mice that recapitulate most of human AD features, and in neuronal cells expressing the amyloid precursor protein with the familial Swedish mutation (APPswe). We examined the impact of the pharmacological and genetic modulation of AMPK-ULK1 cascade on mitochondria structure and functions in APPswe cells. We evaluated the potential beneficial impact of AMPK-ULK1 activation by Metformin (Met) on mitochondria defects, as well as on early- and late-stage AD-related alterationsin vivoandex vivo.ResultsAt first, we show that AMPK-ULK1 cascade is defective in murine and human AD brains as well as in APPswe cells. We then report that Met administration to 3xTgAD mice alleviates the alterations of neuronal mitochondria structure and function and we consolidate these results in cells using both pharmacological and genetic tools to modulate AMPK-ULK1 cascade. In mice brains, Met reduces the early accumulation of APP C-terminal fragments (APP-CTFs) as well as the amyloid beta (Aβ) burden present in aged mice. Mechanistically, we show that Met increases the localization of APP-CTFs within cathepsin D-positive lysosomal compartmentsin vivoand enhances cathepsin D activityin vitro. The reduction of Aβ load by Met occurs through an increased recruitment of Iba1+cells to Aβ plaques and an enhancement of the phagocytic activity of microglia. Accordingly, in symptomatic 3xTgAD mice, Met alleviates microgliosis and astrogliosis, modulates microglia morphology, reduces peripheral proinflammatory cytokines levels, and regulates the expression of a set of inflammatory genes. In addition, Met normalizes dendritic spines shape in organotypic hippocampal slice cultures modeling AD and improves learning performance of 3xTgAD mice.ConclusionsOur study demonstrates potential therapeutic benefits of targeting AMPK-ULK1 cascade to reverse both early and late AD-related alterations, deserving further investigation in fundamental research and in human clinical studies.
Benchmarking of Chromatin Immunoprecipitation (ChIP-Seq) methods in the Pacific oysterMagallana gigas
Authors: Dellong Amelie , Fallet Manon , Stenger Pierre-Louis , Chaparro Cristian , Vidal-Dupiol Jeremie , Clément Julie , Cosseau Céline , Grunau Christoph 
Published: December 2024

AbstractChromatin Immunoprecipitation sequencing (ChIP-seq) is the method of choice to generate chromatin landscapes across genomes. The scarcity of literature on ChIPseq and absence of a canonical “gold standard” method in mollusks and especially the pacific oysterMagallana gigas, prompted us to compare four ChIP-seq methodologies (Native-ChIP, Crosslink-ChIP, ChIPmentation and Cut & Tag) to find the most suitable method for this species. Our results show that Cut & Tag performs best and ChIPmentation worst. We hypothesize that the reason for this lies in a particularly fragile chromatin structure around genes in the oyster.
PSGL-1 excludes HIV Env from virion surface through spatial hindrance involving structural folding of the decameric repeats (DR)
Authors: Tiwari Sameer , Delfing Bryan M. , Han Yang , Lockhart Christopher , Haikerwal Amrita , Waheed Abdul A. , Freed Eric O. , Jafri M. Saleet , Klimov Dmitri , Wu Yuntao 
Published: December 2024

SummaryP-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like surface glycoprotein, is primarily expressed on lymphoid and myeloid cells. PSGL-1 has recently been identified as an HIV restriction factor, blocking HIV infectivity mainly through virion incorporation that sterically hinders virion attachment to target cells. PSGL-1 also inhibits HIV Env incorporation into virions. However, the molecular mechanisms of PSGL-1-mediated Env exclusion remained unclear. Here, we investigated the role of PSGL-1’s extracellular (EC) and intracellular (IC) domains in Env exclusion. We demonstrate that both EC and IC are important for Env exclusion; when EC was deleted, PSGL-1 completely lost its ability to inhibit Env incorporation, whereas when IC was deleted, PSGL-1 partially lost this activity. In addition, when the decameric repeats (DR) were deleted from EC, PSGL-1 also lost its ability to inhibit Env incorporation. Sequential DR deletion mutagenesis further demonstrated that a minimum of 9 DRs is necessary for Env exclusion. Molecular modeling of the DR structure revealed that PSGL-1 mutants with 7 or fewer DRs pose as an extended “rod-like” structure, whereas those with 9 or more DRs collapse into a “coil-like” structure that spatially excludes Env. Our studies suggest a model in which Env exclusion involves Gag-mediated PSGL-1 targeting to the virion assembly site where DR-mediated spatial exclusion blocks Env incorporation.
Fluid intelligence relates to neural measures of cognitive map formation
Authors: Tenderra R.M. , Theves S. 
Published: December 2024

AbstractPsychometric research on intelligence consistently identifies latent factors underlying performance correlations across cognitive tasks, with one general factor (g) explaining most variance and predicting general life outcomes. Their biological basis is yet unresolved, in particular with regard to the neural information processing mechanisms that may underlie intelligence. Here we test the hypothesis that interindividual differences in relational processing, supported by cognitive maps in the hippocampus, are related to fluid intelligence (gf), a statistical approximation of the general factor. Using standardized cognitive tests and fMRI of mnemonic tasks, we demonstrate a positive correlation specifically between gfand map-like relational encoding of task information. This relationship was neither present for non-relational mnemonic responses in the hippocampus nor for less g-related factors. These findings offer first empirical support for a link between neural mechanisms related to relational reasoning and general cognitive performance and probe the presumed relevance of hippocampal coding properties for cognition more broadly.
Biophysical boundaries for dormancy release in sunflower achenes
Authors: Arata Gonzalo Joaquín , Batlla Diego , Riveira-Rubin Mailén , Demkura Patricia Verónica , Mazzobre María Florencia , Rolandelli Guido , Buera María del Pilar , Rodríguez María Verónica 
Published: December 2024

AbstractReactions leading to dormancy release (DR) in “dry”, orthodox seeds are still poorly understood, as well as their dependence on moisture content and temperature. Sunflower achenes were used to explore the effects of MC combined with a wide range of storage temperatures (ST°) on DR dynamics, tested at 10 and 25°C. Embryo sensitivity to abscisic acid, oxygen uptake and ageing indicators were followed and complemented with predicted viability loss dynamics. Water status was addressed with sorption isotherms and the glass transition temperature (Tg). Small variations in MC and ST° had profound effects on achene dormancy and embryo responsiveness to ABA. Using a ‘temperature by humidity’ coordinate system we mapped three regions allowing DR within the glassy, rubbery and fluid states. Full DR (allowing germination at 10 and 25°C) occurred only in the rubbery state (aboveTg), and optimal ST° for full DR dropped from +30 to-18°C with MC increasing from 0.045 to 0.1 gH2O.gDW-1. Differently, under both glassy and fluid states, DR was incomplete (allowing germination at 25°C but not at 10°C) and required warm ST° which also promoted ageing.HighlightSunflower achenes display diverse mechanisms for dormancy release in the “dry” state, depending on the physical state of water produced by different humidity and temperature combinations.
Single-cell analysis of the epigenome and 3D chromatin architecture in the human retina
Authors: Yuan Ying , Biswas Pooja , Zemke Nathan R. , Dang Kelsey , Wu Yue , D’Antonio Matteo , Xie Yang , Yang Qian , Dong Keyi , Lau Pik Ki , Li Daofeng , Seng Chad , Bartosik Weronika , Buchanan Justin , Lin Lin , Lancione Ryan , Wang Kangli , Lee Seoyeon , Gibbs Zane , Ecker Joseph , Frazer Kelly , Wang Ting , Preissl Sebastian , Wang Allen , Ayyagari Radha , Ren Bing 
Published: December 2024

AbstractMost genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute to disease through dysregulation of gene expression, however, deeper understanding of their mechanisms of action has been impeded by an incomplete annotation of the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays to investigate gene expression, chromatin accessibility, DNA methylome and 3D chromatin architecture in human retina, macula, and retinal pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate regulatory elements and characterized their chromatin states in 23 sub-classes of retinal cells. Comparative analysis of chromatin landscapes between human and mouse retina cells further revealed both evolutionarily conserved and divergent retinal gene-regulatory programs. Leveraging the rapid advancements in deep-learning techniques, we developed sequence-based predictors to interpret non-coding risk variants of retina diseases. Our study establishes retina-wide, single-cell transcriptome, epigenome, and 3D genome atlases, and provides a resource for studying the gene regulatory programs of the human retina and relevant diseases.
Motor unit mechanisms of speed control in mouse locomotion
Authors: Thomas Kyle , Gibbs Rhuna , Marques Hugo , Carey Megan R. , Sober Samuel J. 
Published: December 2024

AbstractDuring locomotion, the coordinated activity of dozens of muscles shapes the kinematic features of each stride, including systematic changes in limb movement across walking speed. Motor units, each of which consists of a single motor neuron and the muscle fibers it innervates, contribute to the total activation of each muscle through their recruitment and firing rate when active. However, it remains unknown how the nervous system controls locomotor speed by changing the firing of individual motor units. To address this, we combined quantitative behavioral analysis of mouse locomotion with single motor unit recordings from the lateral and long heads of the triceps brachii, which drive monoarticular extension of the elbow and biarticular movements of the elbow and shoulder, respectively. In contrast to prior studies employing bulk EMG to examine muscle activity, our recordings revealed the diversity of spike patterning across motor units as well as systematic differences in motor unit activity across muscles and locomotor speeds. First, motor unit activity differed significantly across the lateral and long heads, suggesting differential control of these two closely apposed elbow extensor muscles. Second, we found that individual units were recruited probabilistically during only a subset of strides, showing that bulk EMG signals consistently present in every stride in fact reflect stochastically varying subsets of individual motor units. Finally, although recruitment probability and firing rate both increased at faster walking speeds, increases in recruitment were proportionally larger than rate changes, and recruitment of individual units accompanied changes in limb kinematics. Together, these results reveal how the firing of individual motor units varies systematically across muscles and walking speeds to produce flexible locomotor behavior.
Neural mechanisms of attention, not expectation, govern spatial selection by probabilistic cueing
Authors: Sunder Sricharan , Rajendran Kavya , Biswas Mainak , Sridharan Devarajan 
Published: December 2024

AbstractSpatial probabilistic “Posner” cueing is widely employed in studies of endogenous spatial attention. Such cueing guides attention by providing prior knowledge about the likely spatial location of task-relevant events. Yet, it has been compellingly argued that such spatial priors also elicit expectation effects, rendering Posner cueing unsuitable for measuring attentional effects in isolation. We address this debate by combining signal detection theory models of behavior with concurrent electrophysiological recordings, and directly compare Posner cueing effects with those of attention and expectation cueing. Participants performed two tasks: a dual cueing task, with orthogonal relevance (attention) and probability (expectation) cues, as well as a Posner cueing task. Relevance and probability cueing independently modulated distinct behavioral parameters – perceptual sensitivity and decisional criterion, respectively – whereas Posner cueing modulated both sensitivity and criterion. However, only sensitivity modulations by Posner cueing were correlated with those of relevance cueing. Criterion modulations by Posner cueing were uncorrelated with those of probability cueing. Both Posner and relevance cueing, but not probability cueing, modulated various neural markers of spatial attention, including steady-state visually evoked potential (SSVEP) amplitude and alpha-band (8-12 Hz) oscillation power. Representational similarity analysis and cue-label prediction with deep convolutional neural networks revealed dissociable underpinnings of relevance and probability cueing, and identified Posner cueing’s neural representations with those of relevance cueing. Our results address a long-standing debate in the attention literature and clearly demonstrate that spatial selection by probabilistic cueing is governed by neural mechanisms of attention, not expectation.Significance StatementHow does our brain select relevant information for accomplishing task goals? “Posner cueing” is a popular choice for studying brain mechanisms of goal-driven attention in the lab. Posner cues guide attention by providing advance information about the likely location of task-relevant events. Yet, Posner cueing has been criticized because it engages brain mechanisms not only of attention but of event expectation, as well. We address this critique by employing state-of-the-art neural decoding approaches, including deep convolutional neural networks, and show that behavioral and neural underpinnings of Posner cueing closely match those of attention, not expectation. The results address a long-standing debate in the attention literature and validate Posner cueing as a reliable method for measuring attention’s effects in the brain.
Threshold-dependent negative autoregulation of PIF4 gene expression optimizes growth and fitness in Arabidopsis
Authors: Das Sreya , Garhwal Vikas , Mondal Krishanu , Das Dipjyoti , Gangappa Sreeramaiah N. 
Published: December 2024

AbstractPHYTOCHROME INTERACTING FACTOR 4 (PIF4) is a vital transcription factor that controls plant growth by integrating environmental signals like light and temperature. Though upstream regulators of PIF4 are known, transcriptional regulation ofPIF4is poorly understood. Here, we demonstrate that thePIF4undergoes negative autoregulation. We show thatPIF4promoter activity is more in thepif4mutant but significantly reduced inPIF4overexpression transgenic lines. Moreover, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), which enhances PIF4 protein stability, promotes PIF4 autoinhibition. However, Phytochrome B (phyB), a photoreceptor that decreases PIF4 stability, inhibits autoinhibition. We further develop a network-based mathematical model incorporating the PIF4 autoinhibition and other key interactions. Our modeling and data analysis reveals that PIF4 autoregulation depends on a threshold of cellular PIF4 concentration. Our model also successfully predicts the hypocotyl growth andPIF4promoter activity in various light and temperature conditions. Moreover, we show that the transgenic lines with enhanced PIF4 function negatively influence biomass and yield, irrespective of photoperiod and temperature. Together, the negative feedback of PIF4 dampens its own function and restraints unregulated growth. Our study thus elucidates the mechanisms of how the phyB-COP1/DET1-PIF4 module controlsPIF4transcription in tune with the endogenous PIF4 level.
The (α, β)-kBoolean Signatures of Molecular Toxicity: Microcystin as a Case Study
Authors: Moscato Pablo , Jaeger-Honz Sabrina , Haque Mohammad Nazmul , Schreiber Falk 
Published: December 2024

AbstractBackgroundThe (α, β)-k-Feature Set Problem is a combinatorial problem, that has been proven as alternative to typical methods for reducing the dimensionality of large datasets without compromising the performance of machine learning classifiers.ResultWe present a case study that shows that solutions of the (α, β)-k-Feature Set Problem help to identify molecular substructures related to toxicity. The dataset investigated in this study is based on the inhibition of ser/thr-proteinphosphatases by Microcystin (MC) congeners. MC congeners are a class of structurally similar cyanobacterial toxins, which are critical to human consumption.ConclusionWe show that it is possible to identify biologically meaningful toxicity signatures by applying the (α, β)-kfeature sets on extended connectivity fingerprint representations of MC congeners. Boolean rules were derived from the feature sets to classify toxicity and can be mapped on the chemical structure, leading to insights on the absence/presence of substructures that can explain toxicity. The presented method can be applied on any other molecular data set and is therefore transferrable to other use cases.
Predation on scyphozoan polyps and selective nematocyst incorporation dynamics in the aeolid,Caloria militaris
Authors: Dror Hila , Lotan Tamar , Angel Dror 
Published: December 2024

AbstractAeolid nudibranchs are known to prey on various cnidarians and incorporate nematocysts from their prey into their cerata (dorsal appendages) for self-defense. Nematocyst incorporation is selective, and is based on species, diet, prey availability, and predation pressure. This study investigated the interactions between two nudibranch species,Caloria militarisandFlabellina affinis, and scyphozoan polyps from common eastern Mediterranean jellyfish species, includingRhopilema nomadica,Cassiopea andromeda,Phyllorhiza punctata, andAureliasp. Laboratory experiments were used to assess whether these nudibranchs feed on scyphozoan polyps, and if they incorporate the prey nematocysts into the cerata. Results indicate that whileF. affinisavoids scyphozoan polyps,C. militarisconsumes all tested species, and can subsist on them for extended durations (up to 255 days). Predation rates varied among prey species tested, ranging from a mean of 8 to 43.3 polyps day-1. However,C. militarisdoes not store scyphozoan nematocysts. These findings contribute to understanding nudibranch feeding ecology and the potential roles these predators play in regulating jellyfish blooms. Identification of scyphozoan nematocysts in the cerata of predator aeolid nudibranchs is discussed as a means to locate cryptic scyphozoan polyps in the marine environment.
Motor Learning And Savings Of Adaptive Mediolateral Control During Split-Belt Walking
Authors: Nyangau Norah M. , Bogard Alysha T. , Pollet Aviva K. , Pellegrino Logan M. , Tan Andrew Q. 
Published: December 2024

ABSTRACTActive control of frontal plane mechanics regulates balance in destabilizing environments, such as during asymmetric split-belt walking. Compared to sagittal plane mechanics, mediolateral (ML) kinematic and kinetic adaptations to split-belt perturbations are not as extensively reported. Moreover, the associated metabolic cost of these adaptations as well as the retention of previously learned ML adaptations upon re-exposure to the same perturbation have not been concurrently examined. We investigated adaptations in step width and peak ML ground reaction forces (GRF) during an initial and subsequent perturbation in order to characterize motor learning and motor savings, respectively. Additionally, we examined the extent to which a neuroplasticity inducing stimulus, acute intermittent hypoxia (AIH), affected the magnitude of each adaptation. Although we observed bilateral increases in step width during the initial adaptation, only the slow leg significantly reduced step width during the subsequent perturbation. Distinct interlimb differences emerged as only the slow leg modulated ML GRF during the braking phase whereas the fast leg increased ML GRF during the propulsive phase. The AIH group uniquely demonstrated greater motor savings of reduced step width and peak ML GRF strategies during the propulsive phase, suggesting greater retention of prior strategies. Furthermore, we find significant associations between ML kinetic adaptations and reductions in metabolic cost. Together, our findings suggest that unlike the sagittal plane, asymmetrical frontal plane adaptations contribute to ML stability as well as reductions in metabolic cost during split-belt walking. These insights could inform clinical training approaches to improve balance and prevent falls in clinical populations.NEW & NOTEWORTHYWe investigated adaptations in step width and mediolateral ground reaction forces during the braking and propulsive phases of split-belt walking across an initial and subsequent perturbation. We observe that the initial learning and savings of unique interlimb frontal plane coordination strategies contribute to stability and are associated with a reduction in metabolic cost.
Fertilization triggers cytosolic functions and P-body recruitment of the RNA-binding protein Mei2 to drive fission yeast zygotic development
Authors: Araoyinbo Ayokunle , Salat-Canela Clàudia , Vještica Aleksandar 
Published: December 2024

ABSTRACTCompartmentalized regulation of RNAs is emerging as a key driver of developmental transitions, with RNA-binding proteins performing specialized functions in different subcellular compartments. The RNA-binding protein Mei2, which arrests mitotic proliferation and drives zygotic development in fission yeast, was shown to function in the nucleus to trigger meiotic divisions. Here, using compartment-restricted alleles, we report that Mei2 functions in the cytosol to arrest mitotic growth and initiate development. We find that Mei2 is a zygote-specific component of P-bodies that inhibits the translation of tethered mRNAs. Importantly, we show that P-bodies are necessary for Mei2-driven development. Phosphorylation of Mei2 by the inhibitory Pat1 kinase impedes P-body recruitment of both Mei2 and its target RNA. Finally, we establish that Mei2 recruitment to P-bodies and its cytosolic functions, including translational repression of tethered RNAs, depend on the RNA-binding domain of Mei2 that is dispensable for nuclear Mei2 roles. Collectively, our results dissect how distinct pools of an RNA-binding protein control developmental stages and implicate P-bodies as key regulators of gamete-to-zygote transition.