bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between white matter architecture and language lateralisation in the healthy brain
Authors: Andrulyte Ieva , De Bezenac Christophe , Branzi Francesca , Forkel Stephanie J , Taylor Peter N. , Keller Simon S. 
Published: January 2024

AbstractInterhemispheric anatomical asymmetries have long been thought to be related to language lateralisation. Previous studies have explored whether asymmetries in the diffusion characteristics of white matter language tracts are consistent with language lateralisation. These studies, typically with smaller cohorts, yielded mixed results. This study investigated whether connectomic analysis of quantitative anisotropy (QA) and shape features of white matter tracts across the whole brain are associated with language lateralisation. We analysed 1040 healthy individuals from the Human Connectome Project database. Hemispheric language dominance for each participant was quantified using a laterality quotient (LQ) derived from fMRI activation in regions of interest (ROIs) associated with a language comprehension task compared against a math task. A linear regression model was used to examine the relationship between structural asymmetry and functional lateralisation. Connectometry revealed that LQs were significantly negatively correlated with QA of corpus callosum tracts, including forceps minor, body, tapetum, and forceps major, indicating that reduced language dominance (more bilateral language representation) is associated with increased QA in these regions. The QA of the left arcuate fasciculus, cingulum, and right cerebellar tracts was positively associated with LQ, suggesting that stronger structural asymmetry in these tracts may identify left language dominance. Language lateralisation was not significantly associated with the shape metrics (including length, span, curl, elongation, diameter, volume, and surface area) of all white matter tracts. These results suggest that diffusion measures of microstructural architecture, and not the geometric features of reconstructed white matter tracts, are associated with lateralisation of language comprehension functions. People with increased dependence on both cerebral hemispheres for language processing may have more developed commissural fibres, which may support more efficient interhemispheric communication.
Deciphering the astrocytic contribution to learning and relearning
Authors: Squadrani Lorenzo , Wert-Carvajal Carlos , Müller-Komorowska Daniel , Bohmbach Kirsten , Henneberger Christian , Verzelli Pietro , Tchumatchenko Tatjana 
Published: January 2024

AbstractAstrocytes play a key role in the regulation of synaptic strength and are thought to orchestrate synaptic plasticity and memory. Yet, how specifically astrocytes and their neuroactive transmitters control learning and memory is currently an open question. Recent experiments have uncovered an astrocyte-mediated feedback loop in CA1 pyramidal neurons which is started by the release of endocannabinoids by active neurons and closed by astrocytic regulation of the D-serine levels at the dendrites. D-serine is a co-agonist for the NMDA receptor regulating the strength and direction of synaptic plasticity. Activity-dependent D-serine release mediated by astrocytes is therefore a candidate for mediating between long-term synaptic depression (LTD) and potentiation (LTP) during learning. Here, we show that the mathematical description of this astrocytic regulation is consistent with the classic Bienenstock Cooper Munro (BCM) model for synaptic plasticity, which postulated the existence of an activity-dependent LTP/LTD threshold. We show how the resulting mathematical framework can explain the experimentally observed behavioral effects of astrocytic cannabinoid receptor knock-out on mice during a place avoidance task and give rise to new testable predictions about the learning process advancing our understanding of the functional role of neuron-glia interaction in learning.
Transcriptome Dynamics in Mouse Amygdala under Acute and Chronic Stress Revealed by Thiol-labeled RNA Sequencing
Authors: Zhao Dan , Zhang Lu , Yang Yang 
Published: January 2024

AbstractBoth acute and chronic stress have significant impact on brain functions. The amygdala is essential in mediating stress responses, but how its transcriptomic dynamics change under stress remains elusive. To overcome the difficulties in detecting subtle stress-induced changes by evaluating total RNA using classic RNA sequencing, we conducted thiol-labeled RNA sequencing (SLAM-seq). We injected 4-thiouridine (4sU) into mouse amygdala followed by SLAM-seq to detect nascent mRNA induced by acute and chronic restraint stress, and found that SLAM-seq could label actively transcribed genes in the major neuronal and glial subtypes. We also found that acute stress induced active transcription of 6 gamma-aminobutyric acid (GABA) receptors and only 1 glutamate receptor, indicating an imminent increase of inhibitory control in the stressed amygdala. Conversely, chronic stress led to active transcription of 3 glutamate receptors and 4 GABA receptors, suggesting a release of inhibitory control and hyperactivity of the amygdala. SLAM-seq also identified genes associated with myelination under chronic stress, and this finding is confirmed by immunostaining showing increased myelination in chronically stressed amygdala. Additionally, genes detected by SLAM-seq and RNA-seq only partially overlapped, with SLAM-seq particularly sensitive to transcriptional changes in genes with high basal transcription levels. Thus, by applying SLAM-seqin vivo, we obtained a rich dataset of nascently transcribed genes in the amygdala under stress, and revealed distinct transcriptional dynamics associated with acute and chronic stress.
Simulated brain networks reflecting progression of Parkinson’s disease
Authors: Jung Kyesam , Eickhoff Simon B. , Caspers Julian ,   UKD-PD team, Popovych Oleksandr V. 
Published: January 2024

AbstractNeurodegenerative progression of Parkinson’s disease affects brain structure and function and, concomitantly, alters topological properties of brain networks. The network alteration accompanied with motor impairment and duration of the disease is not yet clearly demonstrated in the disease progression. In this study, we aim at resolving this problem with a modeling approach based on large-scale brain networks from cross-sectional MRI data. Optimizing whole-brain simulation models allows us to discover brain networks showing unexplored relationships with clinical variables. We observe that simulated brain networks exhibit significant differences between healthy controls (n=51) and patients with Parkinson’s disease (n=60) and strongly correlate with disease severity and disease duration of the patients. Moreover, the modeling results outperform the empirical brain networks in these clinical measures. Consequently, this study demonstrates that utilizing simulated brain networks provides an enhanced view on network alterations in the progression of motor impairment and potential biomarkers for clinical indices.
Adenomatous polyposis coli (APC) regulates internalization and signaling of the chemorepellent receptor, Roundabout (ROBO) 1
Authors: Huang Yi-Wei , St-Germain Jonathan , Pang Bo Wen , Collins Richard F , Coyaud Etienne , Li Wenjuan , Mohamed Amir , Raught Brian , Grinstein Sergio , Robinson Lisa A 
Published: January 2024

AbstractThe SLIT-ROBO signaling pathway regulates axon guidance and cell migration, and ROBO1 is a receptor for SLIT ligands. ROBO1 undergoes constitutive endocytosis which is enhanced upon SLIT2 binding, but the molecular mechanisms and functional consequences of this process are not well understood. Using pharmacologic inhibitors and molecular techniques, we found that clathrin-mediated endocytosis is necessary for SLIT2-induced inhibition of cell spreading. To explore the underlying mechanisms, we performed BioID to identify ROBO1-interacting proteins whose association with the cytoplasmic domain of ROBO1 is differentially regulated by SLIT2. We discovered that adenomatous polyposis coli (APC), a multifunctional tumor suppressor, constitutively interacts with ROBO1 but dissociates upon binding of SLIT2 and that this dissociation is necessary for clathrin-mediated endocytosis of ROBO1 and subsequent effects on cell morphology. These findings provide new insights into the functional mechanisms by which SLIT2 binding to ROBO1 effects changes in actin cytoskeletal architecture.
Beyond Glycolysis: Aldolase A is a Novel Effector in Reelin Mediated Dendritic Development
Authors: Lagani Gavin D. , Lin Weiwei , Natarajan Sahana , Lampl Noah , Harper Evelyn R. , Emili Andrew , Beffert Uwe , Ho Angela 
Published: January 2024

AbstractReelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with non-canonical receptors and unidentified co-receptors; however, the effects of which are less understood. Using high-throughput tandem mass tag LC-MS/MS-based proteomics and gene set enrichment analysis, we identified both shared and unique intracellular pathways activated by Reelin through its canonical and non-canonical signaling in primary murine neurons during dendritic growth and arborization. We observed pathway crosstalk related to regulation of cytoskeleton, neuron projection development, protein transport, and actin filament-based process. We also found enriched gene sets exclusively by the non-canonical Reelin pathway including protein translation, mRNA metabolic process and ribonucleoprotein complex biogenesis suggesting Reelin fine-tunes neuronal structure through distinct signaling pathways. A key discovery is the identification of aldolase A, a glycolytic enzyme and actin binding protein, as a novel effector of Reelin signaling. Reelin inducedde novotranslation and mobilization of aldolase A from the actin cytoskeleton. We demonstrated that aldolase A is necessary for Reelin-mediated dendrite growth and arborization in primary murine neurons and mouse brain cortical neurons. Interestingly, the function of aldolase A in dendrite development is independent of its known role in glycolysis. Altogether, our findings provide new insights into the Reelin-dependent signaling pathways and effector proteins that are crucial for actin remodeling and dendritic development.SignificanceReelin is an extracellular glycoprotein and exerts its function primarily by binding to the canonical lipoprotein receptors Apoer2 and Vldlr. Reelin is best known for its role in neuronal migration during prenatal brain development. Reelin also signals through a non-canonical pathway outside of Apoer2/Vldlr; however, these receptors and signal transduction pathways are less defined. Here, we examined Reelin’s role during dendritic outgrowth in primary murine neurons and identified shared and distinct pathways activated by canonical and non-canonical Reelin signaling. We also found aldolase A as a novel effector of Reelin signaling, that functions independently of its known metabolic role, highlighting Reelin’s influence on actin dynamics and neuronal structure and growth.
Spring temperature and land use change are associated withRana temporariareproductive success and phenology
Authors: Oliver Kat E. , Harrison Xavier A. 
Published: January 2024

ABSTRACTChemical pollution, land cover change, and climate change have all been established as important drivers of amphibian reproductive success and phenology. However, liQle is known about the relative impacts of these anthropogenic stressors, nor how they may interact to alter amphibian population dynamics. Addressing this gap in our knowledge is important, as it allows us to identify and prioritise the most needed conservation actions. Here, we use long-term datasets to investigate landscape-scale drivers of variation in the reproductive success and phenology of UK Common frog (Rana temporaria) populations. Consistent with predictions, we found that increasing mean temperatures resulted in clear advancements in amphibian breeding phenology: earlier congregation of breedingR. temporaria, earlier initialisation of spawning, and earlier hatching. Temperature and number of frost days also affected rates of spawn mortality. However, temperature increases were also strongly correlated with increases in urban area, arable area, and nitrate levels in the vicinity of spawning grounds. None of these variables could explain variation in the total surface area of spawn present at breeding sites. These findings support previous work linking warming temperatures to shiZ in amphibian breeding phenology, but also highlight the importance of assessing the effect of land use change and pollution on wild amphibian populations. These results have implications for our understanding of the response of wild amphibian populations to climate change, and the management of human-dominated landscapes for declining wildlife populations.
Population Bursts in a Modular Neural Network as a Mechanism for Synchronized Activity in KNDy Neurons
Authors: Blanco Wilfredo , Tabak Joel , Bertram Richard 
Published: January 2024

AbstractThe pulsatile activity of gonadotropin-releasing hormone neurons (GnRH neurons) is a key factor in the regulation of reproductive hormones. This pulsatility is orchestrated by a network of neurons that release the neurotransmitters kisspeptin, neurokinin B, and dynorphin (KNDy neurons), and produce episodic bursts of activity driving the GnRH neurons. We show in this computational study that the features of coordinated KNDy neuron activity can be explained by a neural network in which connectivity among neurons is modular. That is, a network structure consisting of clusters of highly-connected neurons with sparse coupling among the clusters. This modular structure, with distinct parameters for intracluster and intercluster coupling, also yields predictions for the differential effects of the co-released transmitters neurokinin B and dynorphin. In particular, it provides one possible explanation for how the excitatory neurotransmitter neurokinin B and the inhibitory neurotransmitter dynorphin can both increase the degree of synchronization among KNDy neurons.Author summarySince the discovery of a small population of hypothalamic neurons that secrete kisspeptin, neurokinin B, and dynorphin (KNDy neurons), there has been interest in their role as a pacemaker for the pulsatile release of key reproductive hormones. A fundamental question is what mechanism coordinates KNDy neuron activity to generate population bursts. Optical imaging of the KNDy network at single-neuron resolution has revealed that individual KNDy neurons participate in many, but not all, population bursts. It has also shown that the order in which the neurons are recruited in each burst could be highly determined in some animals but not in others. We demonstrate here that these observations can be explained by a neural network with a modular structure. We also show how such a structure can explain the paradoxical finding that both the excitatory neurotransmitter neurokinin B and the inhibitory neurotransmitter dynorphin can act to increase the degree of synchronization among the KNDy neurons.
Neuropeptidergic regulation of neuromuscular signaling in larval zebrafish alters swimming behavior and synaptic transmission
Authors: Dill Holger , Liewald Jana F. , Becker Michelle , Seidenthal Marius , Gottschalk Alexander 
Published: January 2024

SUMMARYThe regulation of synaptic transmission is crucial for plasticity, homeostasis and learning. Chemical synaptic transmission is thus modulated to accommodate different activity levels, which also enables homeostatic scaling in pre- and postsynaptic compartments. In nematodes, cAMP signaling enhances cholinergic neuron output, and these neurons use neuropeptide signaling to modulate synaptic vesicle content. To explore if this mechanism is conserved in vertebrates, we studied the involvement of neuropeptides in cholinergic transmission at the neuromuscular junction of larval zebrafish. Optogenetic stimulation by photoactivated adenylyl cyclase (bPAC) resulted in elevated locomotion as measured in behavioural assays. Furthermore, post-synaptic patch-clamp recordings revealed that in bPAC transgenics, the frequency of miniature excitatory postsynaptic currents (mEPSCs) was increased after photostimulation. These results suggested that cAMP-mediated activation of ZF motor neurons leads to increased fusion of SVs, consequently resulting in enhanced neuromuscular activity. We generated mutants lacking the neuropeptide processing enzyme carboxypeptidase E (cpe), and the most abundant neuropeptide precursor in motor neurons, tachykinin (tac1). Both mutants showed exaggerated locomotion after photostimulation.cpemutants exhibit lower mEPSC frequency during photostimulation and less large-amplitude mEPSCs. Intac1mutants mEPSC frequency was not affected but amplitudes were significantly smaller. Exaggerated locomotion in the mutants thus reflected upscaling of postsynaptic excitability.cpeandtac1mutant muscles expressed more nicotinic acetylcholine receptors (nAChR) on their surface. Thus, neuropeptide signaling regulates synaptic transmitter output in zebrafish motor neurons, and muscle cells homeostatically regulate nAChR surface expression, compensating reduced presynaptic input. This mechanism may be widely conserved in the animal kingdom.
A removable and cosmopolitan dsRNA Toti-like virus causes latent infection in a model diatom strain
Authors: Zhang Jiahuan , Li Chenjie , Xiong Xiaofeng , Guo Kangning , Feng Yanlei , Zhang Huan , Hu Hanhua , Li Xiaobo 
Published: January 2024

AbstractDiatoms contribute to 20% of global primary productivity. Although some diatom viruses have been identified, the molecular mechanisms underlying their interactions with the host remain poorly understood. In this study, we report the discovery of an RNA molecule in the DNA extracts of thePhaeodactylum tricornutumstrain Pt1, which possesses a well-annotated genome and has been used as a diatom model system since 1956. We confirmed this molecule to be a double-stranded linear RNA molecule and, through sequencing, demonstrated it to be a virus in theTotiviridaefamily that is prevalent among marine stramenopiles. We also detected this virus inPhaeodactylum tricornutumstrain Pt3, which was collected in 1930s from a similar geographic location to Pt1, suggesting its prevalence within the region. By employing various inhibitors of the viral RNA-dependent RNA polymerase, we successfully generated a virus-free line isogenic to Pt1, establishing a model system to investigate the impact of RNA viruses on diatom physiology. The virus-free lines did not display obvious growth advantages or defects, indicating a tendency of the virus towards latent infection. Furthermore, we generated a robust antibody against the coat protein of this virus. By performing immunoprecipitation coupled with mass spectrometry, we found that translation-related proteins are enriched as potential interacting partners of the coat protein. Our results suggest that potential viral impacts in molecular research should be considered when Pt1 and Pt3 are used for studying translation-related processes. Additionally, our study unveiled a temperate mode of interaction between viruses and marine algal hosts that differs from the commonly-reported virulent, lytic infections.Highlightsprevalent dsRNA virus belonging to theTotiviridaefamily was discovered in the Pt1 and Pt3 strains of the model diatomPhaeodactylum tricornutum.virus is absent in eight other strains ofP. tricornutum, highlighting the importance of studying multiple accessions.virus can be eliminated using a nucleotide analogue, resulting in a virus-free isogenic strain that allows us to investigate how viruses may affect diatom physiology.robust antibody against the coat protein of this virus was developed to assist mechanistic studies of diatom-virus interactions.
Notch Inhibition Enhances Morphological Reprogramming of microRNA-Induced Human Neurons
Authors: Burbach Kyle F. , Yoo Andrew S. 
Published: January 2024

AbstractAlthough the importance of Notch signaling in brain development is well-known, its specific contribution to cellular reprogramming remains less defined. Here, we use microRNA-induced neurons that are directly reprogrammed from human fibroblasts to determine how Notch signaling contributes to neuronal identity. We found that inhibiting Notch signaling led to an increase in neurite extension, while activating Notch signaling had the opposite effect. Surprisingly, Notch inhibition during the first week of reprogramming was both necessary and sufficient to enhance neurite outgrowth at a later timepoint. This timeframe is when the reprogramming miRNAs, miR-9/9* and miR-124, primarily induce a post-mitotic state and erase fibroblast identity. Accordingly, transcriptomic analysis showed that the effect of Notch inhibition was likely due to improvements in fibroblast fate erasure and silencing of anti-neuronal genes. To this effect, we identifyMYLIP, whose downregulation in response to Notch inhibition significantly promoted neurite outgrowth. Moreover, Notch inhibition resulted in cells with neuronal transcriptome signature defined by expressing long genes at a faster rate than the control, demonstrating the effect of accelerated fate erasure on neuronal fate acquisition. Our results demonstrate the critical role of Notch signaling in mediating morphological changes in miRNA-based neuronal reprogramming of human adult fibroblasts.
Interneuron-like features of microglia in the mouse outer retina
Authors: Toros Sara , Kane Thomas , Hare Aura , Abbar Hassina , Madoo Akshay , De Rossi Giulia , Powell Kate , Rizzi Matteo 
Published: January 2024

AbstractMicroglia have recently been associated with complex functionalities both in the brain and the retina, including in synaptic function and plasticity. While investigating the morphology, protein expression profile and connectivity of microglia in the mouse outer retina, we have found that they closely resemble interneurons in the outer retina of other species. We argue that functional studies are needed to reveal whether they also perform an interneuron-like role in vision.