bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-format attentional template during preparation in human visual cortex
Authors: Chen Yilin , Liu Taosheng , Jia Ke , Theeuwes Jan , Gong Mengyuan 
Published: September 2024

AbstractGoal-directed attention relies on forming internal templates of key information relevant for guiding behavior, particularly when preparing for upcoming sensory inputs. However, evidence on how these attentional templates is represented during preparation remains controversial. Here, we combine functional magnetic resonance imaging (fMRI) with an orientation cueing task to isolate preparatory activity from stimulus-evoked responses. Using multivariate pattern analysis, we found decodable information of the to-be-attended orientation during preparation; yet preparatory activity patterns were different from those evoked when actual orientations were perceived. When perturbing the neural activity by means of a visual impulse (‘pinging’ technique), the preparatory activity patterns in visual cortex resembled those associated with perceiving these orientations. The observed differential patterns with and without the impulse perturbation suggest a predominantly non-sensory format and a latent, sensory-like format of representation during preparation. Furthermore, the emergence of the sensory-like template coincided with enhanced information connectivity between V1 and frontoparietal areas and was associated with improved behavioral performance. This dual-format mechanism suggests that during preparation the brain encodes more detailed template information beyond its immediate use, potentially providing advantages for adaptive attentional control. Consistent with recent theories of non-veridical, ‘good-enough’ attentional template for initial guidance, our findings established a neural basis for implementing two representational formats in different functional states during preparation: a predominantly non-sensory format for guidance and a latent sensory-like format for prospective stimulus processing.
Track-A-Worm 2.0: A Software Suite for Quantifying Properties ofC. elegansLocomotion, Bending, Sleep, and Action Potentials
Authors: Vedantham Kiranmayi , Niu Longgang , Ma Ryan , Connelly Liam , Nagella Anusha , Wang Sijie Jason , Wang Zhao-Wen 
Published: September 2024

AbstractComparative analyses of locomotor behavior and cellular electrical properties between wild-type and mutantC. elegansare crucial for exploring the gene basis of behaviors and the underlying cellular mechanisms. Although many tools have been developed by research labs and companies, their application is often hindered by implementation difficulties or lack of features specifically suited forC. elegans.Track-A-Worm 2.0addresses these challenges with three key components:WormTracker,SleepTracker, andAction Potential (AP) Analyzer.WormTrackeraccurately quantifies a comprehensive set of locomotor and body bending metrics, reliably distinguish between the ventral and dorsal sides, continuously tracks the animal using a motorized stage, and seamlessly integrates external devices, such as a light source for optogenetic stimulation.SleepTrackerdetects and quantifies sleep-like behavior in freely moving animals.AP Analyzerassesses the resting membrane potential, afterhyperpolarization level, and various AP properties, including threshold, amplitude, mid-peak width, rise and decay times, and maximum and minimum slopes. Importantly, it addresses the challenge of AP threshold quantification posed by the absence of a pre-upstroke inflection point.Track-A-Worm 2.0is potentially a valuable tool for manyC. elegansresearch labs due to its powerful functionality and ease of implementation.
Microglia-specific NF-κB signaling is a critical regulator of prion-induced glial inflammation and neuronal loss
Authors: Hay Arielle J. D. , Popichak Katriana A. , Mumford Genova , Shirley Payton , Bian Jifeng , Wolfrath Lauren , Lei Samantha , Eggers Michael , Nicholson Eric M. , Tjalkens Ronald B. , Zabel Mark D. , Moreno Julie A. 
Published: September 2024

AbstractPrion diseases are a group of rare and fatal neurodegenerative diseases caused by the cellular prion protein, PrPC, misfolding into the infectious form, PrPSc, which forms aggregates in the brain. This leads to activation of glial cells, neuroinflammation, and irreversible neuronal loss, however, the role of glial cells in prion disease pathogenesis and neurotoxicity is poorly understood. Microglia can phagocytose PrPSc, leading to the release of inflammatory signaling molecules, which subsequently induce astrocyte reactivity. Animal models show highly upregulated inflammatory molecules that are a product of the Nuclear Factor-kappa B (NF-κB) signaling pathway, suggesting that this is a key regulator of inflammation in the prion-infected brain. The activation of the IκB kinase complex (IKK) by cellular stress signals is critical for NF-κB-induced transcription of a variety of genes, including pro-inflammatory cytokines and chemokines, and regulators of protein homeostasis and cell survival. However, the contribution of microglial IKK and NF-κB signaling in the prion-infected brain has not been evaluated. Here, we characterize a primary mixed glial cell model containing wild-type (WT) astrocytes and IKK knock-out (KO) microglia. We show that, when exposed to prion-infected brain homogenates, NF-κB-associated genes are significantly downregulated in mixed glial cultures containing IKK KO microglia. Mice with IKK KO microglia show rapid disease progression when intracranially infected with prions, including an increase in microglia and reactive astrocytes, and accelerated loss of hippocampal neurons and associated behavioral deficits. These animals display clinical signs of prion disease early and have a 22% shorter life expectancy compared to infected wild-type mice. Intriguingly, PrPScaccumulation was significantly lower in the brains of infected animals with IKK KO microglia compared to age-matched controls, suggesting that accelerated disease is independent of PrPScaccumulation, highlighting a glial-specific pathology.Conversely, primary mixed glia with IKK KO microglia have significantly more PrPScaccumulation when exposed to infected brain homogenates. Together, these findings present a critical role in NF-κB signaling from microglia in host protection suggesting that microglial IKK may be involved in sufficient clearance of prions.
Protonation/deprotonation-driven switch for the redox stability of low-potential [4Fe-4S] ferredoxin
Authors: Wada Kei , Kobayashi Kenji , Era Iori , Isobe Yusuke , Kamimura Taigo , Marukawa Masaki , Nagae Takayuki , Honjo Kazuki , Kaseda Noriko , Motoyama Yumiko , Inoue Kengo , Sugishima Masakazu , Kusaka Katsuhiro , Yano Naomine , Fukuyama Keiichi , Mishima Masaki , Kitagawa Yasutaka , Unno Masaki 
Published: September 2024

AbstractFerredoxin is a small iron-sulfur protein and acts as an electron carrier. Low-potential ferredoxins harbor [4Fe-4S] cluster(s), which play(s) a crucial role as the redox center. Low-potential ferredoxins are able to cover a wide range of redox potentials (−700 to −200 mV); however, the mechanisms underlying the factors which control the redox potential are still enigmatic. Here, we determined the neutron structure of ferredoxin fromBacillus thermoproteolyticus, and experimentally revealed the exact hydrogen-bonding network involving the [4Fe-4S] cluster. The density functional theory calculations based on the hydrogen-bonding network revealed that protonation states of the sidechain of Asp64 close to the [4Fe-4S] cluster critically affected the stability of the reduced state in the cluster. These findings provide the first identification of the intrinsic control factor of redox potential for the [4Fe-4S] cluster in low-potential ferredoxins.
Targeted memory reactivation elicits temporally compressed reactivation linked to spindles
Authors: Abdellahi Mahmoud E. A. , Rakowska Martyna , Treder Matthias S. , Lewis Penelope A. 
Published: September 2024

AbstractMemories reactivate during sleep, however the properties of such reactivation and its relationship to encoding strength and subsequent memory performance are not well understood. We set out to examine memory reactivations associated with a serial reaction time task (SRTT). 48 human participants performed the SRTT, and then slept in the lab while we deliberately induced reactivation in Slow Wave Sleep (SWS) using a Targeted Memory Reactivation (TMR) design. We detected reactivation after TMR cues using multiclass classification that adapted to sleep data by using sleep activity for training and wake activity for testing. We then examined the temporal properties of reactivation in relation to behavioural performance and sleep spindles. In keeping with the rodent literature, the observed reactivation was 3 to 20 times faster than waking activity. Furthermore, we report an inverted-U shaped relationship between TMR-related behavioural improvement and encoding strength, with very strong and very weak memories benefiting little from cueing while medium-strength memories benefit the most. Finally, reactivation was more frequently observed in trials with high sigma power, supporting the idea that sleep spindles are associated with memory reactivation during sleep. These findings bring us closer to understanding the characteristics of human memory reactivation after TMR, demonstrate when cueing is effective, and provide evidence for the positive relationship between the detectability of reactivation and memory consolidation.
Mitochondrial Fatty Acid Oxidation is Stimulated by Red Light Irradiation
Authors: Herrera Manuel Alejandro , Caldeira da Silva Camille C. , Baptista Mauricio S. , Kowaltowski Alicia J. 
Published: September 2024

AbstractThe skin is our largest organ, and also the most exposed to solar radiation. As mitochondria within skin cells are rich in endophotosensitizers such as NADH, FADH2, and cytochromes, we studied the effects of different UV and visible light wavelengths on metabolic fluxes in keratinocytes, the main cell type in the epidermis. We find that 36 J/cm2of UV light (λmaxat 365 nm) leads to a complete inhibition of oxidative phosphorylation. The same light dose at other wavelengths (blue light, 450 nm, and green light, 517 nm) did not affect metabolic fluxes, but reduced cell viability, probably by photosensitizing oxidation. Strikingly, red light (660 nm) not only did not decrease cell viability, but also enhanced cell proliferation as well as basal and maximal oxygen consumption rates for up to two days after irradiation. To uncover the mechanisms in which this unexpected long-lived metabolic enhancement occurred, we measured quantities of oxidative phosphorylation-related proteins and oxygen consumption in permeabilized cells, which were unchanged. This result is indicative of a modulation of cytosolic metabolic processes by red light. Subsequently, we measured glycolytic, glutamine-dependent, and fatty-acid supported metabolic fluxes and determined that red light specifically activates fatty acid oxidation by mitochondria. Overall, our results demonstrate that light modulates oxidative phosphorylation with different effects at distinct wavelengths. Interestingly, we uncover a novel and highly specific effect of red light modulating fatty acid oxidation in keratinocytes, providing a novel mechanistic explanation for the metabolic effects of photobiomodulation.HighlightsDifferent UV and visible light wavelengths affect keratinocytes distinctly: UV leads to cell death and metabolic flux inhibition, while green light decreases viability without affecting oxygen consumption.Surprisingly, red light increases intact cell oxygen consumption up to two days post exposure.Red light exposure does not change the quantity or activity of components of oxidative phosphorylation in mitochondria.Increased mitochondrial respiration and ATP synthesis promoted by red light is fueled by enhanced fatty acid oxidation.
Behavioral Evidence for Two Modes of Attention
Authors: Gupta Akanksha , Matthews Tomas E. , Penhune Virginia B. , Morillon Benjamin 
Published: September 2024

AbstractAttention modulates sensory gain to select and optimize the processing of behaviorally relevant events. It has been hypothesized that attention can operate in either a rhythmic or continuous mode, depending on the nature of sensory stimulation. Despite this conceptual framework, direct behavioral evidence has been scarce. Our study explores when attention operates in a rhythmic mode through a series of nine interrelated behavioral experiments with varying stream lengths, stimulus types, attended features, and tasks. The rhythmic mode optimally operates at approximately 1.5 Hz and is prevalent in perceptual tasks involving long (> 7 s) auditory streams. Our results are supported by a model of coupled oscillators, illustrating that variations in the system’s noise level can induce shifts between continuous and rhythmic modes. Finally, the rhythmic mode is absent in syllable categorization tasks. Overall, this study provides empirical evidence for two modes of attention and defines their conditions of operation.
Distinct basal ganglia decision dynamics under conflict and uncertainty
Authors: Ging-Jehli Nadja R. , Cavanagh James F. , Ahn Minkyu , Segar David J. , Asaad Wael F. , Frank Michael J. 
Published: September 2024

AbstractThe basal ganglia (BG) play a key role in decision-making, preventing impulsive actions in some contexts while facilitating fast adaptations in others. The specific contributions of different BG structures to this nuanced behavior remain unclear, particularly under varying situations of noisy and conflicting information that necessitate ongoing adjustments in the balance between speed and accuracy. Theoretical accounts suggest that dynamic regulation of the amount of evidence required to commit to a decision (a dynamic “decision boundary”) may be necessary to meet these competing demands. Through the application of novel computational modeling tools in tandem with direct neural recordings from human BG areas, we find that neural dynamics in the theta band manifest as variations in a collapsing decision boundary as a function of conflict and uncertainty.We collected intracranial recordings from patients diagnosed with either Parkinson’s disease (n=14) or dystonia (n=3) in the subthalamic nucleus (STN), globus pallidus internus (GPi), and externus (GPe) during their performance of a novel perceptual discrimination task in which we independently manipulated uncertainty and conflict. To formally characterize whether these task and neural components influenced decision dynamics, we leveraged modified diffusion decision models (DDMs). Behavioral choices and response time distributions were best characterized by a modified DDM in which the decision boundary collapsed over time, but where the onset and shape of this collapse varied with conflict. Moreover, theta dynamics in BG structures predicted the onset and shape of this collapse but differentially across task conditions. In STN, theta activity was related to a prolonged decision boundary (indexed by slower collapse and therefore more deliberate choices) during high-conflict situations. Conversely, rapid declines in GPe theta during low conflict conditions were related to rapidly collapsing boundaries and expedited choices, with additional complementary decision bound adjustments during high uncertainty situations. Finally, GPi theta effects were uniform across conditions, with increases in theta prolonging the collapse of decision bounds. Together, these findings provide a nuanced understanding of how our brain thwarts impulsive actions while nonetheless enabling behavioral adaptation amidst noisy and conflicting information.
Mindfulness-based Neurofeedback: A Systematic Review of EEG and fMRI studies
Authors: Treves Isaac N. , Greene Keara D. , Bajwa Zia , Wool Emma , Kim Nayoung , Bauer Clemens C.C. , Bloom Paul A. , Pagliaccio David , Zhang Jiahe , Whitfield-Gabrieli Susan , Auerbach Randy P. 
Published: September 2024

AbstractNeurofeedback concurrent with mindfulness meditation may reveal meditation effects on the brain and facilitate improved mental health outcomes. Here, we systematically reviewed EEG and fMRI studies of mindfulness meditation with neurofeedback (mbNF) and followed PRISMA guidelines. We identified 10 fMRI reports, consisting of 177 unique participants, and 9 EEG reports, consisting of 242 participants. Studies of fMRI focused primarily on downregulating the default-mode network (DMN). Although studies found decreases in DMN activations during neurofeedback, there is a lack of evidence for transfer effects, and the majority of studies did not employ adequate controls, e.g. sham neurofeedback. Accordingly, DMN decreases may have been confounded by general task-related deactivation. EEG studies typically examined alpha, gamma, and theta frequency bands, with the most robust evidence supporting the modulation of theta band activity. Both EEG and fMRI mbNF have been implemented with high fidelity in clinical populations. However, the mental health benefits of mbNF have not been established. In general, mbNF studies would benefit from sham-controlled RCTs, as well as clear reporting (e.g. CRED-NF).
Homoploid Hybridization Resolves the Origin of Octoploid Strawberries
Authors: Fan Zhen , Liston Aaron , Soltis Douglas , Soltis Pamela , Ashman Tia-Lynn , Hummer Kim , Whitaker Vance M. 
Published: September 2024

AbstractThe identity of the diploid progenitors of octoploid cultivated strawberry (Fragaria × ananassa) has been subject to much debate. Past work identified four subgenomes and consistent evidence forF. californica(previously namedF. vescasubsp.bracteata) andF. iinumaeas donors for subgenomes A and B, respectively, with conflicting results for the origins of subgenomes C and D. Here, reticulate phylogeny and admixture analysis support hybridization betweenF. viridisandF. vescain the ancestry of subgenome A, and betweenF. nipponicaandF. iinumaein the ancestry of subgenome B. Using an LTR-age-distribution-based approach, we estimate that the octoploid and its intermediate hexaploid and tetraploid ancestors emerged approximately 0.8, 2, and 3 million years ago, respectively. These results provide an explanation for previous reports ofF. viridisandF. nipponicaas donors of the C and D subgenomes and unify conflicting hypotheses about the evolutionary origin of octoploidFragaria.
Virally-Mediated Enhancement of Efferent Inhibition Reduces Acoustic Trauma in Wild Type Murine Cochleas
Authors: Slika Eleftheria , Fuchs Paul A. , Wood Megan Beers 
Published: September 2024

AbstractNoise-induced hearing loss (NIHL) poses an emerging global health problem with only ear protection or sound avoidance as preventive strategies. In addition, however, the cochlea receives some protection from medial olivocochlear (MOC) efferent neurons, providing a potential target for therapeutic enhancement. Cholinergic efferents release ACh (Acetylycholine) to hyperpolarize and shunt the outer hair cells (OHCs), reducing sound-evoked activation. The (α9)2(α10)3nicotinic ACh receptor (nAChR) on the OHCs mediates this effect. Transgenic knock-in mice with a gain-of-function nAChR (α9L9’T) suffer less NIHL. α9 knockout mice are more vulnerable to NIHL but can be rescued by viral transduction of the α9L9’T subunit. In this study, an HA-tagged gain-of-function α9 isoform was expressed in wildtype mice in an attempt to reduce NIHL. Synaptic integration of the virally-expressed nAChR subunit was confirmed by HA-immunopuncta in the postsynaptic membrane of OHCs. After noise exposure, α9L9’T-HA injected mice had less hearing loss (auditory brainstem response (ABR) thresholds and threshold shifts) than did control mice. ABRs of α9L9’T-HA injected mice also had larger wave1 amplitudes and better recovery of wave one amplitudes post noise exposure. Thus, virally-expressed α9L9’T combines effectively with native α9 and α10 subunits to mitigate NIHL in wildtype cochleas.One Sentence SummaryViral transduction of a gain-of-function nAChR enhances the native cholinergic inhibition to protect the cochlea from noise-induced hearing loss.
Conditional Localization Pharmacology Manipulates the Cell Cycle with Spatiotemporal Precision
Authors: Deng Changfeng , Lan Yung-Chi , Chen Geng-Yuan , Ekeabu Chigozie S. , Chung Megan , Lampson Micheal A. , Chenoweth David M. 
Published: September 2024

AbstractTraditional pharmacology has limited control of drug activity and localization in space and time. Herein, we described an approach for kinase regulation using conditional localization pharmacology (CLP), where an inactive caged inhibitor is localized to a site of interest in a dormant state using intracellular protein tethering. The activity of the inhibitor can be regulated with spatial and temporal precision in a live cellular environment using light. As a proof of concept, a photocaged MPS1 kinase inhibitor (reversine) bearing a Halo-tag ligand tether was designed to manipulate the cell cycle. We demonstrate that this new caged reversine halo probe (CRH) strategy is capable of efficient localization and exceptional spatiotemporal control over spindle assembly checkpoint (SAC) silencing and mitotic exit.
A structural MRI marker predicts individual differences in impulsivity and classifies patients with behavioral-variant frontotemporal dementia from matched controls
Authors: Godefroy Valérie , Durand Anaïs , Simon Marie-Christine , Weber Bernd , Kable Joseph , Lerman Caryn , Bergström Fredrik , Levy Richard , Batrancourt Bénédicte , Schmidt Liane , Plassmann Hilke , Koban Leonie 
Published: September 2024

ABSTRACTImpulsivity and higher preference for sooner over later rewards (i.e., delay discounting) are transdiagnostic markers of many psychiatric and neurodegenerative disorders. Yet, their neurobiological basis is still debated. Here, we aimed at 1) identifying a structural MRI signature of delay discounting in healthy adults, and 2) validating it in patients with behavioral variant frontotemporal dementia (bvFTD)—a neurodegenerative disease characterized by high impulsivity. We used a machine-learning algorithm to predict individual differences in delay discounting rates based on whole-brain grey matter density maps in healthy male adults (Study 1, N=117). This resulted in a cross-validated prediction-outcome correlation ofr=0.35 (p=0.0028). We tested the validity of this brain signature in an independent sample of 166 healthy adults (Study 2) and its clinical relevance in 24 bvFTD patients and 18 matched controls (Study 3). In Study 2, responses of the brain signature did not correlate significantly with discounting rates, but in both Studies 1 and 2, they correlated with psychometric measures of trait urgency—a measure of impulsivity. In Study 3, brain-based predictions correlated with discounting rates, separated bvFTD patients from controls with 81% accuracy, and were associated with the severity of disinhibition among patients. Our results suggest a new structural brain pattern—the Structural Impulsivity Signature (SIS)—which predicts individual differences in impulsivity from whole-brain structure, albeit with small-to-moderate effect sizes. It provides a new brain target that can be tested in future studies to assess its diagnostic value in bvFTD and other neurodegenerative and psychiatric conditions characterized by high impulsivity.