bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of BioID tagging systems in budding yeast and exploring the interactome of the Ccr4-Not complex
Authors: Pfannenstein J. , Tyryshkin M. , Gulden M.E , Doud E.H. , Mosley A. L. , Reese J.C. 
Published: May 2024

AbstractThe modified E. coli biotin ligase BirA* was the first developed for proximity labeling of proteins (BioID). However, it has low activity at temperatures below 37°C, which reduces its effectiveness in organisms growing at lower temperatures, such as budding yeast. Multiple derivatives of the enzymes have been engineered, but a comparison of these variations of biotin ligases has not been reported in Saccharomyces cerevisiae. Here, we designed a suite of vectors to compare the activities of biotin ligase enzymes in yeast. We found that the newer TurboID versions were the most effective at labeling proteins, but they displayed low constitutive activity from biotin contained in the culture medium. We describe a simple strategy to express free BioID enzymes in cells that can be used as an appropriate control in BioID studies to account for the promiscuous labeling of proteins caused by random interactions between bait-BioID enzymes in cells. We also describe chemically-induced BioID systems exploiting the rapamycin-stabilized FRB-FKBP interaction. Finally, we used the TurboID version of the enzyme to explore the interactome of different subunits of the Ccr4-Not gene regulatory complex. We find that Ccr4-Not predominantly labeled cytoplasmic mRNA regulators, consistent with its function in mRNA decay and translation quality control in this cell compartment.
Emerging neurodevelopmental mechanisms in patient induced pluripotent stem cells-derived spheroids modellingSCN1ADravet Syndrome
Authors: Mattei Cristiana , Mao Miaomiao , Byars Sean , Syazwan Erlina Mohamed , Oliva Megan , Karle Timothy , Richards Kay , Scheffer Ingrid , Petrou Steven , Maljevic Snezana 
Published: May 2024

AbstractSCN1Aencodes Naᵥ1.1, a voltage-gated sodium channel preferentially expressed in GABAergic interneurons, and it is the major cause of Dravet Syndrome (DS), a rare condition of developmental and epileptic encephalopathy (DEE). Among over 1000 DS mutations reported to date, almost all causeSCN1Aloss-of function (LoF). A reduction in NaV1.1 function in inhibitory neurons would subsequently cause an over-excitation of glutamatergic neurons resulting in seizures, which are exacerbated by the use of sodium channel blocking common anti-seizure medications (ASM). In this study we generated and assessed 3D spheroids enriched with GABAergic neurons fromSCN1ADS patient to establish a 3D human-derived DS model. To investigate developmental disruptions in DS pathophysiology we profiled the transcriptome of patient-derived spheroids and subsequently, tested the capability of this 3Din vitromodel to reveal the cellular mechanisms of DS and predict drug response. In summary, our patient iPSC-derived neuronal model ofSCN1ADS revealed a profound dysregulation of developmental processes which correlated with functional disruption in GABAergic neurons and predicted response to fenfluramine, an ASM increasingly used for the treatment of DS.
Optimal AAV capsid/promoter combinations to target specific cell types in the common marmoset cerebral cortex
Authors: Matsuzaki Yasunori , Fukai Yuuki , Konno Ayumu , Hirai Hirokazu 
Published: May 2024

AbstractTo achieve cell type-specific gene expression, using target cell-tropic AAV capsids is advantageous. However, their tropism across brain cell types remains unexplored in non-human primates. We assessed the tropism of nine AAV serotype capsids (AAV1, 2, 5, 6, 7, 8, 9, rh.10 (rh10), and DJ) on marmoset cerebral cortical cell types. Marmoset cerebral cortex was injected with different serotype AAVs expressing enhanced GFP (EGFP) by the ubiquitous chicken β-actin hybrid (CBh) promoter. After 4 weeks, all nine AAV capsid vectors, especially AAV9 and AAVrh10, caused highly neuron-selective EGFP expression. Some AAV capsids, including AAV5, caused EGFP expression in oligodendrocytes to a lesser extent, with minimal or no expression in astrocytes and microglia. Different ubiquitous CMV and CAG promoters showed similar neuron-predominant transduction. Conversely, all nine AAV capsid vectors with the astrocyte-specific hGFA(ABC1D) promoter selectively transduced astrocytes, except AAV5, which transduced oligodendrocytes modestly. Oligodendrocyte-specific mouse myeline basic protein (mMBP) promoter in AAV5 vectors transduced oligodendrocytes specifically and efficiently. Our results suggest optimal combinations of capsids and promoters for cell type-specific expression: AAV9 or AAVrh10 and ubiquitous CBh, CMV, or CAG promoter for neuron-specific transduction; AAV2 or 7 and hGFA(ABC1D) promoter for astrocyte-specific transduction; and AAV5 and mMBP promoter for oligodendrocyte-specific transduction.
Circulatory dietary and gut-derived metabolites predict preclinical Alzheimer’s disease
Authors: Connell Emily , Sami Saber , Khondoker Mizanur , Minihane Anne-Marie , Pontifex Matthew G. , Müller Michael , McArthur Simon , Gall Gwenaelle Le , Vauzour David 
Published: May 2024

AbstractA key component of disease prevention is the identification of at-risk individuals. Microbial dysbiosis and microbe-derived metabolites (MDM) can influence the central nervous system, but their role in disease progression and as prognostic indicators is unknown. To identify preclinical factors associated with Alzheimer’s disease (AD), we compared gut microbiome and metabolome profiles of cognitively healthy subjects, subjective cognitive impairment (SCI) participants and mild cognitive impairment (MCI) participants (n=50 per group, matched for age, BMI and sex), targeting metabolites previously associated with cognitive health (TMAO, bile acids, tryptophan,p-cresol and their derivatives). 16S rRNA bacterial microbiome sequencing and targeted LC-MS/MS were employed for faecal microbiome speciation and serum MDM quantification. Microbiome beta diversity differed between healthy controls and SCI participants. Multiple linear regression modelling highlighted five serum metabolites (indoxyl sulfate, choline, 5-hydroxyindole acetic acid, indole-3-propionic acid (IPA) and kynurenic acid) significantly altered in preclinical AD. Neuroprotective metabolites, including choline, 5-hydroxyindole acetic acid and IPA, exhibited lower concentrations in SCI and MCI in comparison to controls, while the cytotoxic metabolite indoxyl sulfate had higher levels. A Random Forest algorithm with multiclass classification confirmed and extended our results, identifying six metabolites (indoxyl sulfate, choline, 5-hydroxyindole acetic acid, IPA, kynurenic acid, kynurenine) as predictors of early cognitive decline, with an area under the curve of 0.74. In summary, a combined statistical and machine learning approach identified MDM as a novel composite risk factor for the early identification of future dementia risk.
Genotype-specific effects of physical activities on self-harm behavior in depressed patients: findings from the UK Biobank
Authors: Jung Jaegyun , Lee Sangyeon , Lee Jeong Ho , Lee Doheon 
Published: May 2024

AbstractBackgroundPhysical activities are widely implemented for non-pharmacological intervention in depression. However, there is little evidence supporting their genotype-specific effectiveness in reducing the risk of intentional self-harm in midlife and late-life depression patients.AimsTo assess whether the specific type and amount of physical activity is associated with the risk of intentional self-harm behavior among patients with depression phenotype.MethodWe developed the bidirectional analytic model to investigate the genotype-specific effectiveness (BAIGE) on UK Biobank. After the genetic stratification on the depression phenotype cohort using hierarchical clustering, multivariable logistic regression models and Cox proportional hazard models were built to investigate the associations between physical activity and the risk of intentional self-harm behavior.ResultsA total of 28,923 subjects with depression phenotype were included in the study. In retrospective cohort analysis, the moderate and highly active groups were at lower risk of hospitalizations (moderate: adjusted odds ratio [OR], 0.77 [95% CI, 0.61-0.98], high: OR, 0.76 [95% CI, 0.60-0.97]). In the follow-up prospective cohort analysis, light-intensity physical activity (LIPA) was associated with a lower risk of hospitalizations in one genetic cluster (adjusted hazard ratio [HR], 0.26 [95% CI, 0.08 – 0.88]), which was distinguished by three genetic variants: rs1432639, rs4543289, and rs11209948. Compliance with the guideline-level moderate-to-vigorous physical activities was not significantly related to the risk of hospitalizations.ConclusionsPhysical activities, particularly a certain amount of light-intensity physical activity, mitigate the risk of hospitalizations due to self-harm in depression patients with a specific genotype.
25-hydroxycholesterol promotes brain endothelial dysfunction by remodelling cholesterol metabolism
Authors: Tapia Victor S. , Withers Sarah E. , Zhou Ran , Bennington Abigail , Hedley Frances , El Khouja Adam , Luka Nadim , Massimo Marco , Crilly Siobhan , Long Katherine R. , Lawrence Catherine B. , Kasher Paul R. 
Published: May 2024

AbstractThe antiviral enzyme cholesterol 25-hydroxylase (CH25H) and its metabolite 25-hydroxycholesterol (25HC), which modulates cholesterol metabolism during infection, have been previously associated with vascular pathology. Viral infections have been linked to risk of intracerebral haemorrhage (ICH) but the molecular mechanisms leading to brain vessel rupture via antiviral responses remain unknown. We hypothesised that the CH25H/25HC pathway may impact neuroendothelial integrity in the context of infection-associated ICH. Here, using a SARS-CoV-2-spike-induced zebrafish ICH model and foetal human SARS-CoV-2-associated cortical tissue containing microbleeds, we identified an upregulation of CH25H in infection-associated cerebral haemorrhage. Using zebrafish ICH models and human brain endothelial cells, we asked whether 25HC may promote neurovascular dysfunction by modulating cholesterol metabolism. We found that 25HC and pharmacological inhibition ofHMGCRby atorvastatin interacted to exacerbate brain bleeding in zebrafish larvae andin vitrobrain endothelial dysfunction.In vitro25HC-induced dysfunction was also rescued by cholesterol supplementation. These results demonstrate that the antiviral factor 25HC can dysregulate brain endothelial function by remodelling cholesterol metabolism. We propose that the CH25H/25HC pathway represents an important component in the pathophysiology of brain vessel dysfunction associated with infection and cholesterol dysregulation in the context of ICH.Summary StatementThe antiviral metabolite 25-hydroxycholesterol dysregulates brain endothelial function by remodelling cholesterol metabolism, thereby providing a mechanistic link between viral infection and brain endothelial dysfunction in conditions such as intracerebral haemorrhage.
Intracranial substrates of meditation-induced neuromodulation in amygdala and hippocampus
Authors: Maher Christina , Tortolero Lea , Cummins Daniel D. , Saad Adam , Young James , Martinez Lizbeth Nunez , Schulman Zachary , Marcuse Lara , Waters Allison , Mayberg Helen S. , Davidson Richard J. , Saez Ignacio , Panov Fedor 
Published: May 2024

ABSTRACTMeditation is an accessible mental practice associated with emotional regulation and well-being. Loving-kindness meditation (LKM), a specific sub-type of meditative practice, involves focusing one’s attention on thoughts of well-being for oneself and others. Meditation has been proven to be beneficial in a variety of settings, including therapeutical applications, but the neural activity underlying meditative practices and their positive effects are not well understood. In particular, it’s been difficult to understand the contribution of deep limbic structures given the difficulty of studying neural activity directly in the human brain. Here, we leverage a unique patient population, epilepsy patients chronically implanted with responsive neurostimulation device that allow chronic, invasive electrophysiology recording to investigate the physiological correlates of loving-kindness meditation in the amygdala and hippocampus of novice meditators. We find that LKM-associated changes in physiological activity specific to periodic, but not aperiodic, features of neural activity. LKM was associated with an increase in γ (30-55 Hz) power and an alternation in the duration of β (13-30 Hz) and γ oscillatory bursts in both the amygdala and hippocampus, two regions associated with mood disorders. These findings reveals the nature of LKM-induced modulation of limbic activity in first-time meditators.SIGNIFICANCE STATEMENTWe leverage rare chronic, invasive electrophysiology recordings while participants engage in loving-kindness meditation to demonstrate that meditation induces neural changes in beta and γ activity in the amygdala and hippocampus of novice meditators. These results build on previous findings in experienced meditators and reveal meditation’s potential for noninvasive neuromodulation of neural mechanisms associated with emotional regulation and mood disorders.
EEG frequency tagging reveals the integration of dissimilar observed actions
Authors: Formica Silvia , Chaiken Anna , Wiersema Jan R. , Cracco Emiel 
Published: May 2024

AbstractExtensive research has demonstrated that visual and motor cortices can simultaneously represent multiple observed actions. This ability undoubtedly constitutes a crucial ingredient for the understanding of complex visual scenes involving different agents. However, it is still unclear how these distinct representations are integrated into coherent and meaningful percepts. In line with studies of perceptual binding, we hypothesized that similar movements would be more easily integrated. To test this hypothesis, we developed an EEG frequency tagging experiment in which two hand movements were displayed simultaneously at two different presentation rates. Crucially, the degree of similarity between the two movements varied along two dimensions, namely action identity (i.e., same or different performed movement), and agent identity (i.e., one agent performing a bimanual movement, or two agents moving each one hand). Contrary to our predictions, we found a larger intermodulation oscillatory component, indexing the integrated processing of the two individual movements, when they were less similar. We propose that integration-by-dissimilarity might serve as a top-down process to solve conflict caused by incongruent movements in a complex social scene.
Connecting the Dots: Approaching a Standardized Nomenclature for Molecular Connectivity Combining Data and Literature
Authors: Reed MB , Cocchi L , Knudsen GM , Sander C , Gryglewski G , Chen J , Volpi T , Fisher P , Khattar N , Silberbauer LR , Murgaš M , Godbersen GM , Nics L , Walter M , Hacker M , Hammers A , Ogden TR , Mann JJ , Biswal B , Rosen B , Carson R , Price J , Lanzenberger R , Hahn A 
Published: May 2024

AbstractPET-based connectivity computation is a molecular approach that complements fMRI-derived functional connectivity. However, the diversity of methodologies and terms employed in PET connectivity analysis has resulted in ambiguities and confounded interpretations, highlighting the need for a standardized nomenclature.Drawing parallels from other imaging modalities, we propose “molecular connectivity” as an umbrella term to characterize statistical dependencies between PET signals across brain regions at the individual level (within-subject). Like fMRI resting-state functional connectivity, “molecular connectivity” leverages temporal associations in the PET signal to derive brain network associations. Another within-subject approach evaluates regional similarities of tracer kinetics, which are unique in PET imaging, thus referred to as “kinetic connectivity”. On the other hand, “molecular covariance” denotes group-level computations of covariance matrices across-subject. Further specification of the terminology can be achieved by including the employed radioligand, such as “metabolic connectivity/covariance” for [18F]FDG as well as “tau/amyloid covariance” for [18F]flutemetamol / [18F]flortaucipir.To augment these distinctions, high-temporal resolution functional [18F]FDG PET scans from 17 healthy participants were analysed with common techniques of molecular connectivity and covariance, allowing for a data-driven support of the above terminology. Our findings demonstrate that temporal band-pass filtering yields structured network organization, whereas other techniques like 3rdorder polynomial fitting, spatio-temporal filtering and baseline normalization require further methodological refinement for high-temporal resolution data. Conversely, molecular covariance from across-subject data provided a simple means to estimate brain region interactions through regularized or sparse inverse covariance estimation.A standardized nomenclature in PET-based connectivity research can reduce ambiguity, enhance reproducibility, and facilitate interpretability across radiotracers and imaging modalities. Via a data-driven approach, this work provides a transparent framework for categorizing and comparing PET-derived connectivity and covariance metrics, laying the foundation for future investigations in the field.
Evidence of spatial periodic firing in the subiculum of mice
Authors: Abad-Perez P. , Scott R. , Borrell V. , Martínez-Otero L. , Brotons-Mas J.R. 
Published: May 2024

AbstractThe subiculum (SUB) is a region located at the core of the hippocampal formation. The SUB receives input from grid cells located in the medial entorhinal cortex (MEC) and from place cells in the CA1 area. Moreover, this structure mediates the output from the hippocampus to cortical and sub-cortical areas involved in the processing of different types of information. Despite the potential relevance of the SUB, its role in memory and spatial coding remains poorly studied. Previous work described a heterogeneous population of SUB spatial neurons, with evidence of its role in coding the geometry of the environment and spatial navigation in darkness. With the aim of further understanding the properties of spatial coding in the SUB, we implanted mice with microdrives carrying tetrodes to target CA1 and the SUB. Apart from the classical place cells described before, we discovered a fraction of SUB pyramidal neurons that generated spatial periodic firing. SUB spatial neurons presented lower spatial resolution and spatial stability than CA1 place cells. The role of spatial periodic neurons in the SUB might be relevant in several computations through the interaction of this region with CA1, the pre-parasubiculum and the MEC.Significance StatementSpatial information coding and memory formation rely on a complex circuit involving the hippocampal formation and multiple types of spatially tuned neurons. For the first time, we found evidence of pyramidal neurons the SUB of mice exhibiting grid-like and periodic firing patterns. Our data support the idea that the SUB may play a role in complex spatial information processing, extending beyond the integration of CA1 unit inputs.
Augmenting visual errors or variability does not enhance motor learning in remote web application tasks
Authors: Nakano Nobuyasu , Murai Akihiko 
Published: May 2024

ABSTRACTLaboratory experiments employing robotic manipulandum are far from achieving their goal of helping people improve their motor learning. Remote experiments using web applications are an effective tool for bridging the gap between robotic manipulandum experiments in the laboratory and general motor tasks outside. However, the influence of interventions that increase error or variability in remote motor tasks on motor learning has not yet been determined. In this study, we aimed to elucidate the effects of interventions that visually increase errors and variability in remote experiments using web applications. In particular, 48 people participated in a web-based study on the cursor-manipulation of motor tasks using laptops. Three motor tasks (visuomotor-rotation reaching, virtual curling, and virtual ball-throwing tasks) were conducted, and each task consisted of 120 trials a day conducted for three days in this study. For each task, no intervention was provided on Day 1 and the intervention to augment motor error or variability was provided on Days 2 and 3. Differences between the groups in post-intervention test trials were examined using statistical analyses. Contrary to our expectations, the interventions of error-augmentation did not exhibit positive effects in Experiments 1 and 2, which could be attributed to a lack of haptic and proprioceptive information or inaccuracies in movement kinematics. In addition, the interventions of variability-augmentation did not exhibit positive effects in Experiment 3, which could be attributed to the complex dynamics in the relationship between perceived body movements and motor outcomes. Further research is required to identify the differences between the conditions when the interventions are effective or ineffective. Moreover, interventions must be developed to further improve general motor skills.
States of functional connectivity flow and their multiplex dynamics in human epilepsy and postictal aphasia
Authors: Pedreschi Nicola , Trebuchon Agnès , Barrat Alain , Battaglia Demian 
Published: May 2024

AbstractThe mechanisms that cause aphasia as a transient post-seizure symptom in epileptic patients are yet unknown. We analyse intracranial EEG (sEEG) recordings of patients suffering from pharmaco-resistant epilepsy with postictal aphasia. We study the Functional Connectivity (FC) between different cortical sites in a time- and frequency-resolved manner, representing each recording as a time-varying, multilayer network (dynamic multiplex). We studied in particular: the rate of overall reconfiguration of links from one frame to the next, or dynamic Functional Connectivity (dFC) speed; and the stability of network modules through time, by means of a dynamic modular Allegiance (dA) analysis. The combination of these two approaches allows identifying states of “Functional Connectivity flow” (beyond connectivity states), defined as epochs in which network reconfiguration occurs with comparable speed and degree of spatio-temporal coordination. Our unsupervised analyses reveal then that high-frequency dFC is slowed down in a long postictal phase lasting well beyond the ictal episodes themselves. Furthermore, a pathological state of slow and poorly structured network flow consistently co-occurs with episodes of aphasia symptoms annotated by the clinicians. In conclusion, our multiplex network dynamics description cast light on functional mechanisms of postictal cognitive dysfunction at the level of individual patients.