bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoring the Multiple Sclerosis Associated Imbalance of Gut Indole Metabolites Promotes Remyelination and Suppresses Neuroinflammation
Authors: Jank Larissa , Singh Saumitra S. , Lee Judy , Dhukhwa Asmita , Siavoshi Fatemeh , Joshi Deepika , Minney Veronica , Gupta Kanak , Ghimire Sudeep , Deme Pragney , Schoeps Vinicius A. , Soman Karthik , Ladakis Dimitrios , Smith Matthew , Borkowski Kamil , Newman John , Baranzini Sergio E. , Waubant Emmanuelle L. , Fitzgerald Kathryn C. , Mangalam Ashutosh , Haughey Norman , Kornberg Michael , Chamling Xitiz , Calabresi Peter A. , Bhargava Pavan 
Published: October 2024

AbstractIn multiple sclerosis (MS) the circulating metabolome is dysregulated, with indole lactate (ILA) being one of the most significantly reduced metabolites. We demonstrate that oral supplementation of ILA impacts key MS disease processes in two preclinical models. ILA reduces neuroinflammation by dampening immune cell activation as well as infiltration; and promotes remyelination andin vitrooligodendrocyte differentiation through the aryl hydrocarbon receptor (AhR). Supplementation of ILA, a reductive indole metabolite, restores the gut microbiome’s oxidative/reductive metabolic balance by lowering circulating indole acetate (IAA), an oxidative indole metabolite, that blocks remyelination and oligodendrocyte maturation. The ILA-induced reduction in circulating IAA is linked to changes in IAA-producing gut microbiota taxa and pathways that are also dysregulated in MS. Notably, a lower ILA:IAA ratio correlates with worse MS outcomes. Overall, these findings identify ILA as a potential anti-inflammatory remyelinating agent and provide insights into the role of gut dysbiosis-related metabolic alterations in MS progression.One Sentence SummaryIndole lactate, a postbiotic metabolite reduced in MS, corrects gut microbiome metabolic imbalances associated with remyelination and neuroinflammation.
Minimally invasive electrocorticography (ECoG) recording in common marmosets
Authors: Spadacenta Silvia , Dicke Peter W. , Thier Peter 
Published: October 2024

AbstractElectrocorticography (ECoG) enables high spatio-temporal resolution recordings of brain activity with excellent signal quality, making it essential for pre-surgical mapping in epilepsy patients and increasingly useful in neuroscience research, including the development of brain-machine interfaces. The relatively minimal cortical convolution in non-human primate (NHP) brains facilitates ECoG recordings, in particular in the common marmoset (Callithrix jacchus), whose lissencephalic (unfolded) brain surface provides broad cortical access. One of the key advantages of ECoG recordings is the ability to study interactions between distant brain regions. The standard approach is the usage of large electrode arrays, which, however, require extended trepanations and a trade-off between size and electrode spacing. This study introduces an alternative ECoG approach for examining interactions between multiple distant cortical areas in marmosets, combining the advantages of circumscribed trepanations with high-density electrode arrays at specific sites of interest. Two adult marmosets underwent ECoG implantation across frontal, temporal, and parietal regions of interest, assessed by circumscribed trepanations to position individual high density electrode arrays. Postoperative monitoring showed rapid recovery and no long-term complications. The animals remained healthy, and stable neural recordings were successfully obtained during behavioral tasks, highlighting the method’s effectiveness for long-term cortical monitoring.
The influence of temporal context on vision over multiple time scales
Authors: Lee Kacie , Rideaux Reuben 
Published: October 2024

ABSTRACTPast sensory experiences influence perception of the present. Multiple research subfields have emerged to study this phenomenon at different temporal scales. These fall into three categories: the influence of immediately preceding sensory events (micro), short sequences of events (meso), and regularities over long sequences of events (macro). In a single paradigm, we examined the influence of temporal context on perception at each scale. We identify two distinct mechanisms that operate across all scales. The first is moderated by attention and supports rapid motor responses to expected events. The second is independent of task-demands and dampens the feedforward neural responses to expected events, leading to unexpected events eliciting earlier and more precise neural representations. We further show that perceptual recall exclusively reflects neural representations during this initial feedforward stage and that serial dependence (recall biases towards previous events) is explained by expectation of sensory stability over time.
Prediction of dynamic balance state and recovery following stroke using fMRI graph analysis
Authors: Symonitz Or , Joubran Katherin , Puzis Rami , Shmuelof Lior 
Published: October 2024

AbstractStroke is associated with damage to neural tissue and is the leading cause of long-term sensory-motor disability in adults. Dynamic balance impairments are one of the most debilitating outcomes of stroke, leading to increased falls and loss of mobility. While the recovery of motor functions following stroke was shown to be affected by the initial brain damage, the ability to predict recovery based on neural markers is limited due to the involvement of multiple brain areas in dynamic balance, and the limited size of available datasets. We apply graph-theory-based neural markers to predict the extent of recovery in the presence of rehabilitative treatment and the passage of time on a dataset of 21 subjects after stroke. We report that global features are more informative than local features, describing individual regions. We also report that recovery level is predicted more accurately (85%) than dynamic balance state (76%). Our results demonstrate the feasibility of graph-based analyses on limited datasets and may contribute to clinical goal setting and to mapping the neural substrates of dynamic balance.
Investigating the Causal Link Between Serum Iron Status and Pernicious Anaemia Risk: A Mendelian Randomisation Study
Authors: Cimadevila Guillermo Comesaña , Thain Alfie , Dib Marie-Joe , Ahmadi Kourosh R 
Published: October 2024

AbstractIntroductionPernicious anaemia (PA) is characterised by vitamin B12deficiency due to autoimmune-mediated destruction of gastric parietal cells and the consequent loss of intrinsic factor. A considerable proportion of PA patients also exhibit iron deficiency (ID), both before or at (20.7-52%) and after (46.4%) PA diagnosis. However, findings from observational studies do not clarify whether ID contributes to PA risk or is a consequence of the PA disease process. Given the high prevalence of ID at PA diagnosis, we hypothesised that reduced iron status may play a causal role in PA risk.MethodologyWe conducted two-sample Mendelian Randomisation (MR) analyses to evaluate the causal effect between systemic iron status and PA risk. Genetic association data for iron status were sourced from the deCODE study. Additionally, PA-relevant associative data with the chosen SNPs were obtained from genome-wide-association-study (GWAS) summary statistics, primarily from R10FinnGenrelease and from the GWAS conducted by Laisk et al. (2021) for replication purposes. Participant data consisted of 3,694 cases of PA and 393,684 controls. Inverse-variance weighted analysis was the primary MR method, with sensitivity analyses including Egger, and weighted-median estimates, additionally to testing for horizontal pleiotropy and heterogeneity.ResultsFour SNPs were strongly associated with systemic iron status and were used as genetic instruments. We found that genetically predicted iron status was not significantly associated with PA risk (odds ratio per 1 standard deviation increase in serum iron: 1.13, 95% confidence interval 0.80-1.58,P=0.49). Sensitivity analyses had consistent results, indicating that MR assumptions were not violated and highlighting a null result subjectivity due to the presence of horizontal pleiotropy and heterogeneity.ConclusionThis is the first MR study investigating the potential causal relationship between iron status and PA risk. Our results show that genetically predicted iron status is not associated with a significantly increased PA risk among individuals of European ancestry. Further research is needed to understand the manifestation of ID in PA.
AI-based deformable hippocampal mesh reflects hippocampal morphological characteristics in relation to cognition in healthy older adults
Authors: Park Wonjung , Valdés Hernández Maria del C. , Kim Jaeil , Muñoz Maniega Susana , Sneden Fraser , Ferguson Karen J. , Bastin Mark E. , Wardlaw Joanna M. , Cox Simon R. , Park Jinah 
Published: October 2024

ABSTRACTMagnetic resonance imaging (MRI)-derived hippocampus measurements have been associated with different cognitive domains. The knowledge of hippocampal structural deformations as we age has contributed to our understanding of the overall aging process. Different morphological hippocampal shape analysis methods have been developed, but it is unclear how their principles relate and how consistent are the published results in relation to cognition in the normal elderly in the light of the new deep-learning-based (DL) state-of-the-art modeling methods. We compared results from analysing the hippocampal morphology using manually-generated binary masks and a Laplacianbased deformation shape analysis method, with those resulting from analysing SynthSeg-generated hippocampal binary masks using a DL method based on the PointNet architecture, in relation to different cognitive domains. Whilst most previously reported statistically significant associations were also replicated, differences were also observed due to 1) differences in the binary masks and 2) differences in sensitivity between the methods. Differences in the template mesh, number of vertices of the template mesh, and their distribution did not impact the results.HighlightsNewdeep-learning-based hippocampal 3D-shape modeling method replicates hippocampal shape reported associations with cognitionNew deep-learning-based hippocampal 3D-shape modeling method has increased sensitivity than a conventional Lapalcian-based deformation methodAccuracy in hippocampal binary masks is crucial in the AI-based shape modeling method
Exploring the roles of memory replay in targeted memory reactivation and birdsong development: Insights from computational models of complementary learning systems
Authors: Yihe Lu , Földes Tamás , Lewis Penelope A 
Published: October 2024

AbstractReplay facilitates memory consolidation in both biological and artificial systems. Using the complementary learning systems (CLS) framework, we study replay in both humans and birds through computational modelling. We investigate impacts of replay triggered by targeted memory reactivation during sleep and experiments examining how sleep affects the development of birdsong in young songbirds. We show that qualitatively realistic sleep effects can be captured by highly abstracted, idealised CLS models. Our modelling sheds theoretical insights on the mechanisms underlying both strengthening and weakening effects of targeted memory reactivation, and supports the empirical hypothesis that replay drives overnight performance deterioration and correlates positively with the final performance in birdsong development.Author summaryTaking a computational approach, we investigated the roles of memory replay in two complementary learning systems (CLS) models capturing realistic sleep effects observed in two real-life experiments on targeted memory reactivation (TMR) and birdsong development respectively. Our two CLS models are abstract and identical in architecture, and they are distinct in terms of where replay is generated. While the TMR model produces replay samples using its hippocampus, the birdsong model does so using the sensorimotor cortex. We found that certain TMR effects could characterise different TMR models, which might account for individual differences in human subjects. The results of the birdsong model support the idea that the dramatic overnight oscillations in performance accuracy which are observed during birdsong development are mainly driven by memory replay, and that long-term performance gain can be achieved despite short-term performance deterioration during the early nights of development. As we studied the two experiments using the unified CLS framework, we discuss how replay contributes to sleep-dependent performance changes from the perspective of systems consolidation.
The functional impact of LGI1 autoantibodies on human CA3 pyramidal neurons
Authors: Monni Laura , Kornau Hans-Christian , Podestà Alice , Stumpf Alexander , Kalbhenn Thilo , Simon Matthias , Sauvigny Thomas , Onken Julia , Prüss Harald , Alle Henrik , Geiger Jörg R.P. , Holtkamp Martin , Schmitz Dietmar , Fidzinski Pawel 
Published: October 2024

AbstractAutoantibodies against leucine-rich glioma inactivated 1 protein (LGI1 mAb) lead to limbic encephalitis characterized by seizures and memory deficits. While animal models provide insights into mechanisms of LGI1 mAb action, species-specific confirmation is lacking. In this study, we investigated the effects of patient-derived LGI1 mAb on human CA3 neurons using culturedex vivoslices. Analysis of intrinsic properties and morphology indicated functional integrity of these neurons under incubation conditions. Human CA3 neurons received spontaneous excitatory currents with large amplitudes and frequencies, suggestive of “giant” AMPA currents. In slices exposed to LGI1 mAb, human CA3 neurons displayed increased neuronal spike frequency, mirroring effects observed with the Kv1.1 channel blocker DTX-K. This increase likely resulted from decreased Kv1.1 channel activity at the axonal initial segment, as indicated by alterations in action potential properties. A detailed analysis revealed differences between LGI1 mAb and DTX-K effects on action potential properties, suggesting distinct mechanisms of action and emphasizing the need for further exploration of downstream pathways. Our findings underscore the importance of species-specific confirmatory studies of disease mechanisms and highlight the potential of human hippocampal slice cultures as a translational model for investigation of disease mechanisms beyond epilepsy, including the effects of pharmacological compounds and autoantibodies.SignificanceThis study advances our understanding of how autoantibodies against the LGI1 protein, known to cause limbic encephalitis, impact human neurons. By using cultured slices of human hippocampus derived from epilepsy’s surgical resections, we were able to observe the direct effects of these autoantibodies on neurons, specifically CA3 pyramidal cells. Our findings reveal that the autoantibodies increase neuronal activity, similar to what is seen with potassium channel blockers and in animal models. This work emphasizes the importance of studying living tissue from the human brain to confirm disease mechanisms, and demonstrates the potential of using human brain slices as a model for exploring not only epilepsy but also other neurological diseases and drug effects.
Orthogonal spectral and temporal envelope representation in auditory cortex
Authors: Takahashi Kuniyuki , Guo Tianrui , Yamagishi Tatsuya , Ohshima Shinsuke , Tsukano Hiroaki , Horii Arata 
Published: October 2024

AbstractSpeech sounds are acoustically composed of two main components: spectral and temporal. The spectral component or carrier frequency is important for pitch detection and is perceived through activity at specific locations on the tonotopic map in the auditory cortex. The temporal envelope—the dynamic changes in sound wave amplitude over time—plays an essential role in speech perception by mediating phoneme recognition. However, how the steepness of the envelope, which shapes the temporal structure, is represented in the auditory cortex remains poorly understood. This study investigates how the steepness of the envelope of sound waves is represented as a functional organization in the mouse auditory cortex, in relation to spectral tonotopic organization. Using macroscale calcium imaging in GCaMP6f-expressing mice, we mapped the auditory cortex’s responses to tones with systematically varying rise-ramp steepness and frequencies. Our findings reveal that, in two primary-like regions of the auditory cortex, the steepness of the rise ramp is orderly mapped orthogonally to the tonotopic gradient, forming a two-dimensional representation on the cortical surface. Conversely, a significant representation of rise-ramp steepness was not detected in higher-order-like auditory regions. These findings suggest that a dichotomous functional organization independently processes temporal envelopes and spectral features within mammalian auditory cortical areas, with functional structures mirroring the two acoustic structures.
The mechanism of spatial pattern transition in motile bacterial collectives
Authors: Saulnier Jean-Baptiste , Romanos Michèle , Schrohe Jonathan , Cuzin Clémence , Calvez Vincent , Mignot Tâm 
Published: October 2024

AbstractUnderstanding how individual behaviours contribute to collective actions is key in biological systems. InMyxococcus xanthus, a bacterial predator, swarming shifts to rippling patterns due to changes in the local environment near prey colonies. Through high-resolution microscopy and theoretical analysis, we demonstrate that two key properties drive this shift: local cellular alignment guided by an extracellular matrix and the ability of cells to reverse to resolve congestion. A tunable refractory period in the reversal system enables collective adaptation, allowing cells to synchronise in rippling and resolve congestion in swarming. These transitions occur without changes in genetic regulation but create stable spatial domains that promote local differentiation, a mechanism of spatial sorting that may be widespread in biology.
Functional interaction between transcription factor Sfp1 and the NuA4 complex in response to nutrient availability
Authors: Xu Ke , Joly Beauparlant Charles , Bianco Stéphanie , Côté Valérie , Hermann Lara , Droit Arnaud , Downey Michael , Nourani Amine , Côté Jacques 
Published: October 2024

AbstractRibosome biogenesis is a crucial process requiring enormous transcriptional output. In budding yeast, the expression of 138 ribosomal protein (RP) genes and over 200 ribosome biogenesis (RiBi) genes is regulated by and intricate network of factors, including the nutrient-sensitive transcription activator Sfp1 and the NuA4 coactivator/acetyltransferase complex. Nutrient starvation or inhibition of TORC1 by rapamycin leads to repression of RP and RiBi genes, in part through blocking Sfp1 nuclear localization and NuA4-dependent chromatin acetylation. Here, we demonstrate that Sfp1 physically interacts with NuA4 in a TORC1-independent manner. Our results indicate that Sfp1, along with NuA4, regulate transcription of RiBi and RP genes via distinct mechanisms depending on promoter architectures. Sfp1 promotes NuA4-dependent histone acetylation at the promoter of RiBi and RP genes without affecting NuA4 recruitment. In contrast, NuA4 does impact Sfp1 binding but specifically at two classes of RP genes. Importantly, we found that NuA4 acetylates Sfp1 at lysines 655 and lysine 657, regulating its function. Cells expressing Sfp1 with acetyl-mimicking mutations exhibit increased expression of RiBi genes while RP genes remain stable. However, the same mutants lead to the loss of Sfp1 binding/activity at RiBi genes when cells are under non-optimal growth conditions. Mimicking constitutive acetylation of Sfp1 also limits the transcriptional burst of RP genes upon addition of glucose. Altogether, these results draw an intricate functional relationship between Sfp1 and NuA4 to control ribosome biogenesis, fine-tuning transcription output in different growth conditions.
Nanoscale 3D DNA tracing reveals the mechanism of self-organization of mitotic chromosomes
Authors: Beckwith Kai Sandvold , Brunner Andreas , Morero Natalia Rosalia , Jungmann Ralf , Ellenberg Jan 
Published: October 2024

SummaryHow genomic DNA is folded during cell division to form the characteristic rod-shaped mitotic chromosomes essential for faithful genome inheritance is a long-standing open question in biology. Here, we use nanoscale DNA-tracing in single dividing cells to directly visualize how the 3D fold of genomic DNA changes during mitosis, at scales from single loops to entire chromosomes. Our structural analysis reveals a characteristic genome scaling minimum at 6-8 Mbp in mitosis. Combined with data-driven modeling and molecular perturbations, we can show that very large and strongly overlapping loops formed by Condensins are the fundamental structuring principle of mitotic chromosomes. These loops compact chromosomes locally and globally to the limit set by chromatin self-repulsion. The characteristic length, density and increasingly overlapping structure of mitotic loops we observe in 3D, fully explain how the rod-shaped mitotic chromosome structure emerges by self-organization during cell division.
Making Neurobots and Chimerical Ctenophores
Authors: Moroz Leonid L , Norekian Tigran P. 
Published: October 2024

AbstractMaking living machines using biological materials (cells, tissues, and organs) is one of the challenges in developmental biology and modern biomedicine. Constraints in regeneration potential and immune self-defense mechanisms limit the progress in the field. Here, we present unanticipated features related to self-recognition and ancestral neuro-immune architectures of new emerging reference species - ctenophores or comb jellies. These are descendants of the earliest survival metazoan lineage with unique tissues, organs and independent origins of major animal traits such as neurons, muscles, mesoderm, and through-gut. Thus, ctenophores convergently evolved complex organization, compared to bilaterians. Nevertheless, their neural and immune systems are likely functionally coupled, enabling designs and experimental construction of hybrid neural systems and even entire animals. This report illustrates impressive opportunities to build both chimeric animals and neurobots using ctenophores as models for bioengineering. The obtained neurobots and chimeric animals from three ctenophore species (Bolinopsis, Mnemiopsis, andPleurobrachia) were able to be autonomous and survive for days. In sum, the unification of biodiversity, cell biology, and neuroscience opens unprecedented opportunities for experimental synthetic biology.