bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoamine-induced diacylglycerol signaling rapidly accumulates Unc13 in nanoclusters for fast presynaptic potentiation
Authors: Blaum Natalie , Ghelani Tina , Götz Torsten , Chronister Keagan S. , Bengochea Mercedes , Christensen Christian F. , Moulin Thiago C. , Ceresnova Livia , Kern Hanna , Thomas Ulrich , Heine Martin , Sigrist Stephan J. , Walter Alexander M. 
Published: January 2025

AbstractNeuromodulators control mood, arousal, and behavior by inducing synaptic plasticity via G-protein coupled receptors. Long-term potentiation of presynaptic neurotransmitter release requires structural changes, but how fast potentiation is achieved within minutes remains enigmatic. Using theDrosophila melanogasterneuromuscular junction, we show that on the timescale of one minute, octopamine, the invertebrate analog of nor-epinephrine, rapidly potentiates evoked neurotransmitter release by a G protein coupled pathway involving presynaptic OAMB receptors and phospholipase C. No changes of presynaptic calcium influx were seen, but confocal signals of the release factor Unc13A and the scaffolding protein Bruchpilot increased within one minute of octopamine treatment. On the same timescale, live, single-molecule imaging of endogenously tagged Unc13 revealed its instantly reduced motility and its increased concentration in synaptic nanoclusters with potentiation. Presynaptic knockdown of Unc13A fully blocked fast potentiation and removal of its N-terminal localization sequence delocalized the protein fragment to the cytosol, but it was rapidly recruited to the plasma membrane by DAG analog phorbol esters and octopamine, pointing to a role in C-terminal domains. Point mutation of endogenous Unc13 disrupting diacylglycerol-binding to its C1 domain blocked plasticity-induced nanoscopic enrichment and synaptic potentiation. The mutation increased basal neurotransmission but reduced Unc13 levels, revealing a gain of function and potential homeostatic compensation. The mutation also blocked phorbol ester-induced potentiation, decreased the calcium-sensitivity of neurotransmission and caused short-term synaptic depression. At the organismal level, the mutation reduced locomotion and survival while enhancing reproduction. Thus, the Unc13 C1 domain mediates acute subsynaptic compaction of Unc13 under monoamine-induced potentiation and influences short-term plasticity, locomotion, reproduction, and survival.
How Intrinsic Neural Timescales Relate To Event-Related Activity – Key Role For Intracolumnar Connections
Authors: Çatal Yasir , Wolman Angelika , Buccellato Andrea , Keskin Kaan , Northoff Georg 
Published: January 2025

AbstractThe relationship of the brain’s intrinsic neural timescales (INTs) during the resting state with event-related activity in response to external stimuli remains poorly understood. Here, we bridge this gap by combining computational modeling with magnetoencephalography (MEG) data to investigate the relation of intrinsic neuronal timescales (INT) with task-related activity, e.g., event-related fields (ERFs). Using the Jansen-Rit model, we first show that intracolumnar (and thus intra-regional) excitatory and inhibitory connections (rather than inter-regional feedback, feedforward and lateral connections between the columns of different regions) strongly influence both resting state INTs and task-related ERFs. Secondly, our results demonstrate a positive relationship between the magnitude of event-related fields (mERFs) and INTs, observed in both model simulations and empirical MEG data collected during an emotional face recognition task. Thirdly, modeling shows that the positive relationship of mERF and INT depends on intracolumnar connections through observing that the correlation between them disappears for fixed values of intracolumnar connections. Together, these findings highlight the importance of intracolumnar connections as a shared biological mechanism underlying both the resting-state’s INTs and the task-state’s event-related activity including their interplay.
Respiration facilitates behaviour during multisensory integration
Authors: Saltafossi Martina , Zaccaro Andrea , Kluger Daniel S. , Perrucci Mauro Gianni , Ferri Francesca , Costantini Marcello 
Published: January 2025

AbstractThe brain processes information from the external environment alongside signals generated by the body. Among bodily rhythms, respiration emerges as a key modulator of sensory processing. Multisensory integration, the non-linear combination of information from multiple senses to reduce environmental uncertainty, may be influenced by respiratory dynamics. This study investigated how respiration modulates reaction times and multisensory integration in a simple detection task. Forty healthy participants were presented with unimodal (Auditory, Visual, Tactile) and bimodal (Audio-Tactile, Audio-Visual, Visuo-Tactile) stimuli while their respiratory activity was recorded. Results revealed that reaction times systematically varied with respiration, with faster responses during peak inspiration and early expiration but slower responses during the expiration-to-inspiration transition. Applying the race model inequality approach to quantify multisensory integration, we found that Audio-Tactile and Audio-Visual stimuli exhibited the highest integration during the expiration-to-inspiration phase. These findings conceivably reflect respiration phase-locked changes in cortical excitability which in turn, orchestrates multisensory integration. Interestingly, participants also tended to adapt their respiratory cycles, aligning response onsets preferentially with early expiration. This suggests that, rather than a mere bottom-up mechanism, respiration is actively adjusted to maximise the signal-to-noise balance between interoceptive and exteroceptive signals.
Genes responsible for the formation of asymmetrical mandibular teeth in the giant mealworm beetle,Zophobas atratus
Authors: Toga Kouhei , Yokoi Kakeru , Togawa Toru 
Published: January 2025

ABSTRUCTThe mandibles of coleopteran insects are typical examples of external morphological asymmetry in animals. The developmental molecular mechanisms underlying the external morphological asymmetry remain to be elucidated compared to those of the internal asymmetric organ. In the tenebrionid beetle,Zophobas atratus, the inner teeth of adult mandibles are asymmetric, while the pupal mandibles are nearly symmetric. The asymmetric morphogenesis is assumed to be caused by the left-right regulatory differences of inner teeth formation, but even the developmental mechanisms involved in the inner teethper seremains unknown. In this study, we investigated the morphogenetic process involved in the formation of inner teeth and searched for genes responsible for this process. Morphological observation showed that the inner teeth of adults formed during 0-5 days after pupal molting. Left mandibles possessed the characteristic second inner teeth, whereas the right mandibles exhibited invaginations between apical and second inner teeth. We performed RNAi for candidate genes and successfully identified four genes (paired, alistaless, Lim1, andmlpt) involved in the formation of inner teeth. Among them,mlptRNAi had a strong effect on the morphology of the right mandibles, suggesting its involvement in the asymmetrical formation of mandibles.
Association between theta-band resting-state functional connectivity and declarative memory abilities in children
Authors: Gander Soléane , Rouge Coralie , Peiffer Anna , Wens Vincent , Tiège Xavier De , Urbain Charline 
Published: January 2025

AbstractDeclarative memory formation critically relies on the synchronization of brain oscillations in the theta (4–8 Hz) frequency band within specific brain networks. The development of this capacity is closely linked to the functional organization of these networks already at rest. However, the relationship between theta-band resting-state functional connectivity and declarative memory abilities remains unexplored in children. Here, using magnetoencephalography, we examined the association between declarative memory performance and pre-learning resting-state functional connectivity across frequency bands in 32 school-aged children. Declarative memory was assessed as the percentage of correct retrieval of 50 new associations between non-objects and magical functions, while resting-state functional connectivity was measured through power envelope correlation of the theta, alpha, low and high beta frequency bands. We found that stronger theta-band resting-state functional connectivity within occipito-temporo-frontal networks correlated with better declarative memory retrieval, while no correlation was observed in the alpha and beta frequency bands. These findings suggest that the functional brain architecture at rest, specifically involving theta-band oscillations, supports declarative memory in children. This mechanism may facilitate the subsequent rapid transformation of sensory input into visuo-semantic representations, highlighting the critical role of theta-band connectivity in early cognitive development.
Secreted Frizzled-Related Protein 1a regulates hematopoietic development in a dose-dependent manner
Authors: Ide Amber D. , Carpenter Kelsey A. , Elaswad Mohamed , Opria Katherine , Marcellin Kendersley , Gilliland Carla , Grainger Stephanie 
Published: January 2025

ABSTRACTHematopoietic stem and progenitor cells (HSPCs) arise only during embryonic development, and their identity specification, emergence from the floor of the dorsal aorta, and proliferation are all tightly regulated by molecular mechanisms such as signaling cues. Among these, Wnt signaling plays an important role in HSPC specification, differentiation, and self-renewal, requiring precise modulation for proper development and homeostasis. Wnt signaling is initiated when a Wnt ligand binds to cell surface receptors such as those encoded by thefrizzledgene family, activating intracellular signaling pathways that regulate gene expression. Secreted frizzled-related proteins (Sfrps) are known modulators of Wnt signaling, acting as both agonists and antagonists of this pathway. Yet,in vivofunctions of Sfrps in HSPC development remain incompletely understood. Here, we demonstrate that Sfrp1a regulates zebrafish HSPC development and differentiation in a dose-dependent manner. In Sfrp1a loss of function animals, we observe an increase in HSPCs, an upregulation of canonical Wnt signaling, and a decrease in differentiation into both lymphoid and myeloid lineages. Conversely, at low-dosesfrp1aoverexpression, there is a decrease in HSPCs and an increase in lymphoid differentiation. High-dosesfrp1aoverexpression phenocopies the loss of function animals, with an increase in HSPCs, increased canonical Wnt signaling, and decreased lymphoid and myeloid differentiation. These findings highlight the importance of dose-dependent modulation of Sfrps, paralleling what is observed in hematopoietic cancers where SFRP1 loss-of-function and gain-of-function variants can drive tumorigenesis.One sentence summarySfrp1a is required for hematopoietic stem cell development.
Seeking rhythmic patterns in microglial cells within the circadian pineal gland from male rats
Authors: Freites Carlos L. , Avila Martin , Amiotti Juan B. , Muñoz Estela M. 
Published: January 2025

AbstractMicroglia, the innate immune cells of the brain, constitute a highly dynamic cell population that displays several functions influenced by the light:dark (L:D) cycle. Within the pineal gland (PG), a key organ of the circadian timing system, microglia actively participate in its development and homeostasis. However, little is known about their rhythmic features in this circadian organ. This study aimed to elucidate morphological and functional phenotypes of pineal microglial cells at two time points of the L:D cycle. We performed immunofluorescence staining and confocal microscopy on paraffin-embedded pineal sections from 3– and 18-month-old Wistar rats, analyzing samples collected at midday (ZT6) and midnight (ZT18). Our results showed that the density and spatial distribution of IBA1+microglial cells did not vary between ZT6 and ZT18 in the 3-month-old PG. However, these cells exhibited reduced size and amoeboid-like shapes, along with a reduction in the expression of the phagocytosis inhibitor SIRP alpha, at ZT18 compared to ZT6. Moreover, IBA1+cells were immunoreactive for the lysosomal marker CD68 and the autophagic marker LC3B at both ZTs. Additionally, contacts with PAX6+cells were detected in the two ZTs analyzed. Interestingly, IBA1+cells showed attenuated or abolished rhythmicity in morphological parameters and SIRP alpha expression levels in the 18-month-old PG. Our findings suggest that microglia undergo transitions into alerted states at night, characterized by small, rounded shapes and enhanced phagocytic capacity. This adaptation likely prepares them to respond to potential invading agents and other insults in the PG, which could impact the nocturnal melatonin production.Key pointsMicroglia within the rat pineal gland exhibit daily morphological and functional adaptations, enhancing their effectivity to respond against potential challenges in a time-dependent manner.Oscillatory features of pineal microglia diminish with aging, suggesting an attenuation of their functions.Nocturnal reactivity of microglia within the pineal organ may influence its physiology, potentially affecting melatonin synthesis.
iAPEX: Improved APEX-based proximity labeling for subcellular proteomics using an enzymatic reaction cascade
Authors: Sroka Tommy J. , Sanwald Lea K. , Prasai Avishek , Hoeren Josefine , von der Malsburg Karina , Chaumet Valerie , Haberkant Per , Feistel Kerstin , Mick David U. 
Published: January 2025

ABSTRACTAscorbate peroxidase (APEX) is a versatile labeling enzyme used for live-cell proteomics at high spatial and temporal resolution. However, toxicity of its substrate hydrogen peroxide and background labeling by endogenous peroxidases limit its use toin vitrostudies of specific cell types. By combining APEX2 with a D-amino acid oxidase to locally produce hydrogen peroxide, we establish a more versatile, improved APEX (iAPEX) workflow that minimizes hydrogen peroxide toxicity and reduces non-specific background labeling. We employ iAPEX to perform live-cell proteomics of a cellular microdomain, the primary cilium, in previously inaccessible cell lines, leading to the identification of new ciliary proteins. Our study robustly validates common ciliary proteins across two distinct cell lines, while observed differences may reflect heterogeneity in primary cilia proteomes. iAPEX proximity labeling inXenopus laevisprovides a proof-of-concept for futurein vivoapplications.
Epigenome-wide analysis reveals novel DNA methylation signatures significantly associated with the infant pupillary light reflex, a candidate intermediate phenotype for autism
Authors: Fish Laurel A. , Gliga Teodora , Gui Anna , Ali Jannath Begum , Mason Luke , Johnson Mark H. , Charman Tony , Falck-Ytter Terje , Jones Emily J. H. , Kandaswamy Radhika , Happé Francesca , Wong Chloe C. Y. 
Published: January 2025

AbstractAutism is a highly heterogeneous neurodevelopmental condition, currently diagnosed based on behavioural characteristics. Candidate early intermediate phenotypes, such as the Pupillary Light Reflex (PLR), a reflexive constriction of the pupil in response to increased optical luminance, may provide insights into etiological factors and potential biomarkers, such as DNA methylation (DNAm), involved in the emergence of autism. We conducted epigenome-wide DNAm association analyses of 9-, 14-, 24-month PLR onset latency and constriction amplitude in a sample of 51 infants enriched for autism family history, using buccal DNA collected at 9-months.Our epigenome-wide analysis (EWAS) identified four stringently significant differentially methylated probes (p< 2.4 × 10−7) associated with cross-section PLR latency measurements at 14– and 24-months, and with 14-to 24-month PLR latency developmental change. Differentially methylated probes associated with PLR amplitude were identified, but at a less stringent discovery threshold (p< 5 × 10−5). Our region analyses identified several significant differentially methylated regions associated with both PLR latency and amplitude Downstream exploratory pathway analysis identified enrichment for multiple developmental biological processes, as well as several susceptibility genes to autism and related neurodevelopmental conditions includingNR4A2, HNRNPU and NAV2. Our findings provide novel insight into the role of DNAm in PLR development and illuminate biological mechanisms underpinning altered PLR in infancy in emerging autism.
Non-mutated human tau stimulates Alzheimer’s disease-relevant neurodegeneration in a microglia-dependent manner
Authors: Roy Ethan R. , Wang Qiang , Huang Kexin , Li Sanming , Fan Yuanyuan , Escobar Estrella , Huang Shuning , Herrera Juan J. , Li Wenbo , Pridans Clare , Zhou Xiaobo , Ju Cynthia , Cao Wei 
Published: January 2025

AbstractThe accumulation of abnormal, non-mutated tau protein is a key pathological hallmark of Alzheimer’s disease (AD). Despite its strong association with disease progression, the mechanisms by which tau drives neurodegeneration in the brain remain poorly understood. Here, we selectively expressed non-mutated or mutated human microtubule-associated protein tau (hMAPT) in neurons across the brain and observed neurodegeneration in the hippocampus, especially associated with non-mutated human tau. Single-nuclei RNA sequencing confirmed a selective loss of hippocampal excitatory neurons by the wild-type tau and revealed the upregulation of neurodegeneration-related pathways in the affected populations. The accumulation of phosphorylated tau was accompanied by cellular stress in neurons and reactive gliosis in multiple brain regions. Notably, the lifelong absence of microglia significantly and differentially influenced the extent of neurodegeneration in the hippocampus and thalamus. Therefore, our study established an AD-relevant tauopathy mouse model, elucidated both neuron-intrinsic and neuron-extrinsic responses, and highlighted critical and complex roles of microglia in modulating tau-driven neurodegeneration.
High Performance protocol for ultra-short DNA sequencing using Oxford Nanopore Technology (ONT)
Authors: Žemaitis Lukas , Palepšienė Rūta , Juzėnas Simonas , Alzbutas Gediminas , Burgi Pierre-Yves , Heinis Thomas , Charmet Jérôme , Angeloni Suter Silvia , Jost Martin , Raišutis Renaldas , Simmel Friedrich , Galminas Ignas 
Published: January 2025

AbstractIn recent years, Oxford Nanopore Technologies (ONT) has gained substantial attention across various domains of nucleic acids’ research, owing to its unique advantages over other sequencing platforms. Originally developed for long-read sequencing, ONT technology has evolved, with recent advancements enhancing its applicability beyond long reads to include short, synthetic DNA-based applications. However, sequencing short DNA fragments with nanopore technology often results in lower data quality, likely due to a lack of protocols optimised for these fragment sizes. To address this challenge, we refined the standard ONT library preparation protocol to improve its performance for ultra-short DNA targets. Utilising the same core reagents required for conventional ONT workflows, we introduced targeted alterations to enhance compatibility with shorter fragment lengths. We then benchmarked these adjustments against libraries prepared using the standard ONT protocol. Here, we present a comprehensive, step-by-step protocol that is accessible to researchers of varied technical expertise, facilitating high-quality sequencing of ultra-short DNA fragments. This protocol represents a significant improvement in sequencing quality for short DNA fragments using ONT technology, broadening the range of possible applications.Graphical abstract
Characterization of the Gastrointestinal Tract Holstein x Angus Cross Cattle Microbiome During Harvest after Feed Withdrawal
Authors: Costello M.K. , McClure J.C. , Brown J.A. , Mantovani H.C. , Ricke S.C. 
Published: January 2025

AbstractStress during the beef pre-harvest period can induce an inflammatory response and acidotic conditions in the gastrointestinal tract (GIT), which affects the gastrointestinal tract microbiome. The objective of this study was to characterize the status of the GIT microbiome at harvest in beef cattle entering a small USDA processing facility. Nine beef cattle were shipped from a producer in Columbia County, WI to the USDA processing facility at University of Wisconsin-Madison and were harvested across four dates. Digesta samples were collected from eight GIT locations: rumen solids, rumen liquids, abomasum, duodenum, jejunum, ileum, cecum, and large intestines. After DNA extraction with the DNeasy Blood & Tissue Kit, the V4 region of the 16S rRNA gene was amplified and sequenced on the Illumina MiSeq platform. Sequences were analyzed for alpha and beta diversity metrics (ANOVA and ADONOS), core microbiome, ANCOM, and co-occurrence network analyses. Harvest date and GIT location had a significant impact on microbial diversity and community composition (P<0.05), and there was an interaction between GIT location and harvest date (P<0.05). Taxonomic composition shifted throughout the GIT, thoughPrevotellaandTreponemawere core members in several different GIT locations. The co-occurrence analysis revealed microorganisms potentially associated with clinical infections, such asMoryellain the rumen andAcinetobacterin the hindgut, were considered keystone species. These results suggest that the pre-harvest period may negatively impact the beef cattle GIT microbiome. Modulating the GIT microbiome during the pre-harvest period may offer an opportunity to improve food safety.
Attentional enhancement and suppression of stimulus-synchronized BOLD oscillations
Authors: Rafeh Reebal W. , Ngo Geoffrey N. , Muller Lyle E. , Khan Ali R. , Menon Ravi S. , Mur Marieke , Schmitz Taylor W. 
Published: January 2025

AbstractVisual cortical neurons synchronize their firing rates to periodic visual stimuli. EEG is commonly used to study directed attention by frequency-tagging brain responses to multiple stimuli oscillating at different frequencies, but is limited by its coarse spatial resolution. Here we leverage frequency-tagging fMRI (ft-fMRI) to study the influence of directed attention on the fine-grained spatiotemporal dynamics of competing stimulus-driven visual cortical oscillations. Our analysis reveals that distinct populations of visual cortical neurons exhibit in-phase (enhancing) or anti-phase (suppressive) synchronization with the oscillating stimuli. Directed attention homogeneously increases the amplitude of anti-phase BOLD oscillations across the visual hierarchy, consistent with a distributed suppressive field. In contrast, attentional modulation of in-phase BOLD oscillations increases hierarchically from V1 to hV4. The strength of anti-phase, but not in-phase, modulation predicted psychophysical correlates of attentional performance. Our results strongly corroborate the biased competition model of attention and unveil a novel BOLD correlate of attentional suppression.