bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of prefrontal couplings by prior belief-related responses in ventromedial prefrontal cortex
Authors: Wang Bin A. , Drammis Sabrina , Hummos Ali , Halassa Michael M. , Pleger Burkhard 
Published: July 2023

AbstractHumans and animals can maintain constant payoffs in an uncertain environment by steadily re-evaluating and flexibly adjusting current strategy, which largely depends on the interactions between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). While the ventromedial PFC (vmPFC) represents the level of uncertainty (i.e., prior belief about external states), it remains unclear how the brain recruits the PFC-MD network to re-evaluate decision strategy based on the uncertainty. Here, we leverage nonlinear dynamic causal modeling on fMRI data to test how prior belief-dependent activity in vmPFC gates the information flow in the PFC-MD network when individuals switch their decision strategy. We show that the prior belief-related responses in vmPFC had a modulatory influence on the connections from dorsolateral PFC (dlPFC) to both, lateral orbitofrontal (lOFC) and MD. Bayesian parameter averaging revealed that only the connection from the dlPFC to lOFC surpassed the significant threshold, which indicates that the weaker the prior belief, the less was the inhibitory influence of the vmPFC on the strength of effective connections from dlPFC to lOFC. These findings suggest that the vmPFC acts as a gatekeeper for the recruitment of processing resources to re-evaluate the decision strategy in situations of high uncertainty.Author SummaryPrefrontal cortex (PFC) together with the mediodorsal thalamus (MD) jointly establish computations critical for behavioral adaptations. While the task uncertainty (i.e., prior belief) was represented by the ventromedial PFC (vmPFC), it remains unclear how the PFC-MD network reallocates the processing resources to re-evaluate decision strategy under uncertainty. Here we filled this gap by leveraging the Bayesian hierarchical modelling and nonlinear dynamic causal modelling in an associative learning task. We found that in situations of high uncertainty, the prior belief-related responses in vmPFC significantly strengthened effective connectivity from the dorsolateral PFC to the orbitofrontal cortex, but not to the MD. The findings provide evidence for the role of vmPFC in driving the re-evaluation of the decision strategy during behavioral adaptations in situations of uncertainty.
The Nucleoporin Nup153 Is the Anchor for Kif1a during Basal Nuclear migration in Brain Progenitor Cells
Authors: Falnikar Aditi , Quintremil Sebastian , Helmer Paige , Vallee Richard B. 
Published: July 2023

ABSTRACTRadial glial progenitors (RGPs) are highly elongated epithelial cells that give rise to most stem cells, neurons, and glia, in the vertebrate cerebral cortex. During development the RGP nuclei exhibit a striking pattern of cell cycle-dependent oscillatory movements known as interkinetic nuclear migration (INM), which we previously found to be mediated during G1 by the kinesin Kif1a, and during G2 by cytoplasmic dynein, recruited to the nuclear envelope by the nucleoporins RanBP2 and Nup133. We now identify Nup153 as a nucleoporin anchor for Kif1a, responsible for G1-specific basal nuclear migration, providing a complete model for the mechanisms underlying this basic, but mysterious behavior, with broad implications for understanding brain development.
GRouNdGAN: GRN-guided simulation of single-cell RNA-seq data using causal generative adversarial networks
Authors: Zinati Yazdan , Takiddeen Abdulrahman , Emad Amin 
Published: July 2023

AbstractWe introduce GRouNdGAN, a gene regulatory network (GRN)-guided causal implicit generative model for simulating single-cell RNA-seq data,in-silicoperturbation experiments, and benchmarking GRN inference methods. Through the imposition of a user-defined GRN in its architecture, GRouNdGAN simulates steady-state and transient-state single-cell datasets where genes are causally expressed under the control of their regulating transcription factors (TFs). Training on three experimental datasets, we show that our model captures non-linear TF-gene dependences and preserves gene identities, cell trajectories, pseudo-time ordering, and technical and biological noise, with no user manipulation and only implicit parameterization. Despite imposing rigid causality constraints, it outperforms state-of-the-art simulators in generating realistic cells. GRouNdGAN learns meaningful causal regulatory dynamics, allowing sampling from both observational and interventional distributions. This enables it to synthesize cells under conditions that do not occur in the dataset at inference time, allowing to performin-silicoTF knockout experiments. Our results show thatin-silicoknockout of cell type-specific TFs significantly reduces cells of that type being generated. Interactions imposed through the GRN are emphasized in the simulated datasets, resulting in GRN inference algorithms assigning them much higher scores than interactions not imposed but of equal importance in the experimental training dataset. Benchmarking various GRN inference algorithms reveals that GRouNdGAN effectively bridges the existing gap between simulated and biological data benchmarks of GRN inference algorithms, providing gold standard ground truth GRNs and realistic cells corresponding to the biological system of interest. Our results show that GRouNdGAN is a stable, realistic, and effective simulator with various applications in single-cell RNA-seq analysis.
The components of an electrical synapse as revealed by expansion microscopy of a single synaptic contact
Authors: Cárdenas-García Sandra P. , Ijaz Sundas , Pereda Alberto E. 
Published: July 2023

ABSTRACTMost nervous systems combine both transmitter-mediated and direct cell-cell communication, known as ‘chemical’ and ‘electrical’ synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a ‘gap junction’ (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact defines the anatomical limits of a synapse. Expansion microscopy of these contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact’s surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area works as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of AJs. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.
How Veeries vary: Whole genome sequencing resolves fine-scale genetic structure in a long-distance migratory bird,Catharus fuscescens
Authors: Kimmitt Abigail A. , Pegan Teresa M. , Jones Andrew W. , Winker Kevin , Winger Benjamin M. 
Published: July 2023

AbstractFine-scale resolution of spatial genetic structure is important for understanding a species’ evolutionary history and contemporary genetic diversity. For high-latitude species with high dispersal ability, such as long-distance migratory birds, populations typically exhibit little genetic structure due to high gene flow and recent postglacial expansion. Some migratory birds, however, show high breeding site fidelity, which might reduce gene flow such that population genetic structure could be detectable with sufficient genomic data. We sequenced over 120 low-coverage whole genomes from across the breeding range of a long-distance migratory bird, the Veery (Catharus fuscescens). As this species’ breeding range extends across both historically glaciated and unglaciated regions in North America, we evaluated whether contemporary patterns of structure and genetic diversity are consistent with historical population isolation in glacial refugia. We found strong evidence for isolation by distance across the breeding range, as well as significant population structure between southern Appalachian and northern populations. However, patterns of genetic diversity did not support southern Appalachia as a glacial refugium. Resolution of isolation by distance across the breeding range was sufficient to assign likely breeding origins of individuals sampled in this species’ poorly understood South American nonbreeding range, demonstrating the potential to assess migratory connectivity in this species using genomic data. Overall, our findings suggest that isolation by distance yields subtle associations between genetic structure and geography across the breeding range even in the absence of obvious historical vicariance or contemporary barriers to dispersal.
Molecular characterization of nodose ganglia development reveals a novel population of Phox2b+ glial progenitors in mice
Authors: Lowenstein Elijah D. , Misios Aristotelis , Buchert Sven , Ruffault Pierre-Louis 
Published: July 2023

AbstractThe vagal ganglia, comprised of the superior (jugular) and inferior (nodose) ganglia of the vagus nerve, receive somatosensory information from the head and neck, or viscerosensory information from the inner organs, respectively. Developmentally, the cranial neural crest gives rise to all vagal glial cells and to neurons of the jugular ganglia, while the epibranchial placode gives rise to neurons of the nodose ganglia. Crest-derived nodose glial progenitors can additionally generate autonomic neurons in the peripheral nervous system, but how these progenitors generate neurons is unknown. Here, we found that some Sox10+ neural crest-derived cells in, and surrounding, the nodose ganglion transiently expressed Phox2b, a master regulator of autonomic nervous system development, during early embryonic life. Our genetic lineage tracing analysis revealed that despite their common developmental origin and extreme spatial proximity a substantial proportion of glial cells in the nodose, but not in the neighboring jugular ganglia, have a history of Phox2b expression. Lastly, we used single cell RNA-sequencing (scRNA-seq) to demonstrate that these progenitors give rise to all major glial subtypes in the nodose ganglia, including Schwann cells, satellite glia and glial precursors, and mapped their spatial distribution byin situhybridization. Our work demonstrates that these crest- derived nodose glial progenitors transiently express Phox2b, give rise to the entire complement of nodose glial cells and display a transcriptional program that may underlie their bipotent nature.Significance statementThe nodose ganglia contain sensory neurons that innervate many inner organs and play key roles in homeostatic behaviors such as digestion, regulation of blood pressure and heart rate, and breathing. Nodose sensory neurons are supported by nodose glial cells, which are understudied compared to their neuronal neighbors. Specifically, the genetic program governing their development is not fully understood. Here, we uncover a transcriptional program unique to nodose glial cells (transient expression of Phox2b) that resolves the 40-year-old finding that nodose glial progenitors can also give rise to autonomic neurons (whose development depends on Phox2b expression). Lastly, we leveraged single cell RNA-sequencing to identify the four major subtypes of nodose glial cells and used subtype specific marker genes to map their spatial distribution.
Emotional state dynamics impacts temporal memory
Authors: Wang Jingyi , Lapate Regina C. 
Published: July 2023

AbstractEmotional fluctuations are ubiquitous in everyday life, but precisely how they sculpt the temporal organization of memories remains unclear. Here, we designed a novel task—the Emotion Boundary Task—wherein participants viewed sequences of negative and neutral images surrounded by a color border. We manipulated perceptual context (border color), emotional valence, as well as the direction of emotional-valence shifts (i.e., shifts from neutral-to-negative and negative-to-neutral events) to create encoding events comprised of image sequences with a shared perceptual and/or emotional context. We measured memory for temporal order and subjectively remembered temporal distances for images processedwithinandacrossevents. Negative images processed within events were remembered as closer in time compared to neutral ones. In contrast, temporal distance was remembered as longer for images spanning neutral-to-negative shifts— suggesting temporal dilation in memory with the onset of a negative event following a previously-neutral state. The extent of this negative-picture induced temporal dilation in memory correlated with dispositional negativity across individuals. Lastly, temporal order memory was enhanced for recently presented negative (compared to neutral) images. These findings suggest that emotional-state dynamics matters when considering emotion-temporal memory interactions: While persistent negative events may compress subjectively remembered time, dynamic shifts from neutral to negative events produce temporal dilation in memory, which may be relevant for adaptive emotional functioning.
Interferon-γ lowers tumour growth by increasing glycolysis and lactate production in a nitric oxide-dependent manner: implications for cancer immunotherapy
Authors: Chattopadhyay Avik , Jagdish Sirisha , Karhale Aagosh Kishore , Ramteke Nikita S. , Zaib Arsha , Nandi Dipankar 
Published: July 2023

AbstractInterferon-gamma (IFN-γ), the sole member of the type-II interferon family, is well known to protect the host from infectious diseases as well as mount anti-tumour responses. The amounts of IFN-γ in the tumour microenvironment determine the host responses against tumours; however, several tumours employ evasive strategies by responding to low IFN-γ signalling. In this study, the response of various tumour cell lines to IFN-γ was studiedin vitro. IFN-γ-activation increases glycolytic flux and reduces mitochondrial function in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner in the H6 hepatoma tumour cell line. The higher glycolysis further fuelled NO and ROS production, indicating a reciprocal regulation. These processes are accompanied by Hypoxia inducing factor (HIF)-1αstabilization and HIF-1α-dependent augmentation of the glycolytic flux. The IFN-γ enhancement of lactate production also occurred in other NO-producing cell lines: RAW 264.7 monocyte/macrophage and Renca renal adenocarcinoma. However, two other tumour cell lines, CT26 colon carcinoma and B16F10 melanoma, did not produce NO and lactate upon IFN-γ-activation. HIF-1α stabilization upon IFN-γ-activation led to lower cell growth of B16F10 but not CT26 cells. Importantly, the IFN-γ-activation of both CT26 and B16F10 cells demonstrated significant cellular growth reduction upon metabolic rewiring by exogenous administration of potassium lactate. Clinical studies have shown the crucial roles of IFN-γ for successful cancer immunotherapies involving checkpoint inhibitors and chimeric antigen receptor T cells. The positive implications of this study on the metabolic modulation of IFN-γ activation on heterogeneous tumour cells are discussed.
The impact of incidental anxiety on the neural signature of mentalizing
Authors: Chang Li-Ang , Engelmann Jan B. 
Published: July 2023

AbstractWhile the effects of anxiety on various cognitive processes, including memory, attention, and learning, have been relatively well documented, the neurobiological effects of anxiety on social cognitive processes remain largely unknown. We address this gap using threat-of-shock to induce incidental anxiety while participants performed two false-belief tasks, a standard and an economic-games version. During belief formation and belief inferences, regions in a canonical social cognition network showed activation reflecting mentalizing, including the temporoparietal junction (TPJ), precuneus, and dorsomedial prefrontal cortex (dmPFC). At the same time, we found threat-related suppression of social cognition regions during belief inferences. A conjunction analysis confirmed that a network of regions was simultaneouslyengagedduring mentalizing andsuppressedby anxiety: bilateral TPJ, bilateral IFG, and putamen. We examined how threat impacted the connectivity between seed regions from the conjunction analyses and its targets. During belief formation, we found that anxiety suppressed the connectivity between the precuneus seed and two key mentalizing nodes, the dmPFC and right TPJ. Moreover, during belief inferences threat specificallty suppressed belief-based connectivity between putamen and its targets in IPS and dlPFC, and dispositional distress significantly modulated threat-related suppression of connectivity between the left TPJ seed and left IPS. Our results highlight important effects of incidental and dispositional anxiety on specific nodes of the social cognition network. Taken together, our study uncovers novel interactions between the reward, social cognition, and attentional systems, indicating that social cognitive processes rely on support from other large-scale networks, and that these network interactions are disrupted under incidental anxiety.
ZBTB48 is a pioneer factor regulating B-cell-specific CIITA expression
Authors: Rane Grishma , Kuan Vivian L. S. , Wang Suman , Huang Mok Michelle Meng , Khanchandani Vartika , Hansen Julia , Norvaisaite Ieva , Yong Wai Khang , Jahn Arne , Mukundan Vineeth , Shi Yunyu , Osato Motomi , Li Fudong , Kappei Dennis 
Published: July 2023

SUMMARYCIITA is the master regulator of MHC II gene expression and hence the adaptive immune response. CIITA expression itself is tightly regulated by three cell type-specific promoters, pI, pIII, and by pIV, and can also be induced by IFNγ in non-immune cells. While key regulatory elements have been identified within these promoters, knowledge of transcription factors regulating CIITA is incomplete. Here, we demonstrate that the telomere-binding protein and transcriptional activator ZBTB48 directly binds to both the critical activating elements within CIITA pIII and is essential for its gene expression. ZBTB48 establishes open chromatin at CIITA pIII upstream of activating H3K4me3 modifications both priming CIITA transcription for IFNγ-induction and ensuring constitutive expression in primary murine B cells. Hence, ZBTB48 acts as a molecular on-off-switch for B-cell-specific CIITA expression.
Motor, somatosensory, and executive cortical areas directly modulate firing activity in the auditory midbrain
Authors: Gartside Sarah E , Rees Adrian , Olthof Bas MJ 
Published: July 2023

AbstractWe have recently reported that the central nucleus of the inferior colliculus (the auditory midbrain) is innervated by glutamatergic pyramidal cells originating not only in auditory cortex (AC) but also in multiple ‘non-auditory’ regions of the cerebral cortex. Using optogenetics and electrical stimulation, we investigated the functional properties of these descending connections in vivo in anaesthetised rats. A retrograde virus encoding green fluorescent protein (GFP) and channelrhodopsin (ChR2) injected into the central nucleus of the inferior colliculus (ICC), labelled discrete groups of cells in multiple areas of the cerebral cortex. Light stimulation of AC and M1 caused local activation of cortical neurones and increased the firing rate of neurones in ICc indicating a direct excitatory input from AC and M1 to ICC. Electrical stimulation of M1, secondary motor, somatosensory and prefrontal cortical regions evoked short, fixed latency firing events in ICC as well as longer latency, longer duration increases in firing activity. The short latency events were singular spikes of consistent shape and size likely resulting from monosynaptic excitation of individual ICC units. The longer latency responses comprised multiple units and spikes occurred with significant temporal jitter suggesting polysynaptic activation of local circuits within the ICC. The probability of the monosynaptic event, the magnitude of the polysynaptic response, and the area of ICC affected were dependent on the stimulus current. Our data are consistent with cortical regions exerting an important excitatory direct and indirect regulation of ICc neurones.Significance statementWe have recently described inputs from motor, somatosensory, and executive cortices to the inferior colliculus (IC, auditory midbrain). Here we provide functional evidence for such connections. Optogenetics, using a retrograde virus encoding channelrhodopsin injected into IC revealed a direct excitatory influence of neurones in auditory and motor cortices on firing in IC. Electrical stimulation of discrete cortical regions revealed that multiple non-auditory cortical regions have a direct monosynaptic excitatory influence on neurones in the IC which, in turn, activates local circuits increasing the firing probability of multiple neurones in the IC. This is the first evidence for circuitry by which auditory processing can be influenced at an early stage by activity in the sensory, motor and executive domains.