bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foraging task specialization in honey bees (Apis mellifera): the contribution of floral rewards on the learning performance of pollen and nectar foragers
Authors: Moreno Emilia , Arenas Andrés 
Published: November 2023

ABSTRACTSocial insects live in communities where cooperative actions heavily rely on the individual cognitive abilities of their members. In the honey bee (Apis mellifera), the specialization in nectar or pollen collection is associated with variations in gustatory sensitivity, affecting both associative and non-associative learning. Gustatory sensitivity fluctuates as a function of changes in motivation for the specific floral resource throughout the foraging cycle, yet differences in learning abilities between nectar and pollen foragers at the onset of recollection remains unexplored. Here, we examined nectar and pollen foragers captured upon arrival at food sources. We subjected them to an olfactory PER conditioning using a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen as a co-reinforcement. For non-associative learning, we habituated foragers with a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen, followed by dishabituation tests with either S50% or S10%+P. Our results indicate that pollen foragers show lower performance than nectar foragers when conditioned with S10%. Interestingly, performance improves to levels similar to those of nectar foragers when pollen is included as rewarding stimulus (S10%+P). In non-associative learning, pollen foragers tested with S10%+P displayed a lower degree of habituation than nectar foragers and a higher degree of dishabituation when pollen was used as the dishabituating stimulus (S10%+P). Altogether, our results support the idea that pollen and nectar honey bee foragers differ in their perception of rewards, leading to inter-individual differences in learning that contribute to foraging specialization.
Gene Expression Meta-Analysis Reveals Aging and Cellular Senescence Signatures in Scleroderma-associated Interstitial Lung Disease
Authors: Yang Monica M. , Lee Seoyeon , Neely Jessica , Hinchcliff Monique , Wolters Paul J. , Sirota Marina 
Published: November 2023

AbstractAging and cellular senescence are increasingly recognized as key contributors to pulmonary fibrosis. However, our understanding in the context of scleroderma associated interstitial lung disease (SSc-ILD) is limited. To investigate, we leveraged previously established lung aging and cell-specific senescence signatures to determine their presence and potential relevance to SSc-ILD. We performed a gene expression meta-analysis of lung tissue from 38 SSc-ILD and 18 healthy controls and found markers (GDF15, COMP, CDKN2A) and pathways (p53) of senescence were significantly increased in SSc-ILD. When probing the established aging and cellular senescence signatures, we found epithelial and fibroblast senescence signatures had a 3.6-fold and 3.7-fold enrichment respectively in the lung tissue of SSc-ILD and that lung aging genes (CDKN2A, FRZB, PDE1A, NAPI12)were increased in SSc-ILD. These signatures were also enriched in SSc skin and associated with degree of skin involvement (limited vs. diffuse cutaneous). To further support these findings, we examined telomere length (TL), a surrogate for aging, in lung tissue and found independent of age, SSc-ILD had significantly shorter telomeres than controls in type II alveolar cells in the lung. TL in SSc-ILD was comparable to idiopathic pulmonary fibrosis, a disease of known aberrant aging. Taken together, this study provides novel insight into the possible mechanistic effects of accelerated aging and aberrant cellular senescence in SSc-ILD pathogenesis.
Dissecting the neuronal mechanisms of invariant word recognition
Authors: Agrawal Aakash , Dehaene Stanislas 
Published: November 2023

AbstractLearning to read places a strong challenge on the visual system. Years of expertise lead to a remarkable capacity to separate highly similar letters and encode their relative positions, thus distinguishing words such as FORM and FROM invariantly over a large range of sizes and absolute positions. How neural circuits achieve invariant word recognition remains unknown. Here we address this issue through computational modeling and brain imaging. We first trained deep neural network models to recognize written words, then analyzed the reading-specialized units that emerged in deep layers. With literacy, units became sensitive to specific letter identities and their distance from the blank space at the left or right of a word, thus acting as “space bigrams” encoding ordinal position using an approximate number code. Using 7T functional MRI and magnetoencephalography in adults, we localized the predicted ordinal code anatomically (visual word form area) and temporally (∼220ms). The proposed neuronal mechanism for invariant word recognition can explain reading errors and makes precise predictions about how position-invariant neural codes arise in brains and artificial systems.
Using Extracellular miRNA Signatures to Identify Patients with LRRK2-Related Parkinson’s Disease
Authors: Braunger Luca Jannik , Knab Felix , Gasser Thomas 
Published: November 2023

AbstractBackgroundMutations in the Leucine Rich Repeat Kinase 2 gene are highly relevant in both sporadic and familial cases of Parkinson’s disease. Specific therapies are entering clinical trials but patient stratification remains challenging. Dysregulated microRNA expression levels have been proposed as biomarker candidates in sporadic Parkinson’s disease.ObjectiveIn this proof-of concept study we evaluate the potential of extracellular miRNA signatures to identify LRRK2-driven molecular patterns in Parkinson’s disease.MethodsWe measured expression levels of 91 miRNAs via RT-qPCR in ten individuals with sporadic Parkinson’s disease, tenLRRK2mutation carriers and eleven healthy controls using both plasma and cerebrospinal fluid. We compared miRNA signatures using heatmaps and t-tests. Next, we applied group sorting algorithms and tested sensitivity and specificity of their group predictions.ResultsmiR-29c-3p was differentially expressed betweenLRRK2mutation carriers and sporadic cases, with miR-425-5p trending towards significance. Individuals clustered in principal component analysis along mutation status. Group affiliation was predicted with high accuracy in the prediction models (sensitivity up to 89%, specificity up to 70%). miRs-128-3p, 29c-3p, 223-3p and 424-5p were identified as promising discriminators among all analyses.ConclusionsLRRK2 mutation status impacts the extracellular miRNA signature measured in plasma and separates mutation carriers from sporadic Parkinson’s disease patients. Monitoring LRRK2 miRNA signatures could be an interesting approach to test drug efficacy of LRRK2-targeting therapies. In light of small sample size, the suggested approach needs to be validated in larger cohorts.
Cdc73 majorly regulates apoptosis-inducing factor (AIF1) inSaccharomyces cerevisiaevia the H3K36 methylation
Authors: Saha Nitu , Acharjee Santoshi , Tomar Raghuvir Singh 
Published: November 2023

AbstractAIF1overexpression is intimately linked to the sensitivity of the yeast cells towards hydrogen peroxide or acetic acid. Therefore, studying the mechanism of its regulation in the cell would provide a significant understanding of the factors ultimately guiding yeast apoptosis. In this report, we establish the time-dependent induction ofAIF1in hydrogen peroxide stress. Additionally, theAIF1expression in hydrogen peroxide is mediated by two transcription factors, Yap5 (DNA binding) and Cdc73 (non-DNA binding). Furthermore, substituting the H3K36 residue with another significantly abrogates theAIF1expression. However, substituting H3K4 or H3K79 with A does not affect theAIF1expression level under hydrogen peroxide stress. Altogether, the significant reduction ofAIF1expression incdc73Δ cells plausibly reflects the reduced H3K36me3 modification and is independent of the H3K4me3 modification.
Progressively shifting patterns of co-modulation among premotor cortex neurons carry dynamically similar signals during action execution and observation
Authors: Zhao Zhonghao , Schieber Marc H. 
Published: November 2023

ABSTRACTMany neurons in the premotor cortex show firing rate modulation whether the subject performs an action or observes another individual performing a similar action. Although such “mirror neurons” have been thought to have highly congruent discharge during execution and observation, many if not most actually show non-congruent activity. Studies of neuronal populations active during both execution and observation have shown that the most prevalent patterns of co-modulation—captured as neural trajectories—pass through subspaces which are shared in part, but in part are visited exclusively during either execution or observation. These studies focused on reaching movements for which low-dimensional neural trajectories exhibit comparatively simple dynamical motifs. But the neural dynamics of hand movements are more complex. We developed a novel approach to examine prevalent patterns of co-modulation during execution and observation of a task that involved reaching, grasping, and manipulation. Rather than following neural trajectories in subspaces that contain their entire time course, we identified time series of instantaneous subspaces, calculated principal angles among them, sampled trajectory segments at the times of selected behavioral events, and projected those segments into the time series of instantaneous subspaces. We found that instantaneous neural subspaces most often remained distinct during execution versus observation. Nevertheless, latent dynamics during execution and observation could be partially aligned with canonical correlation, indicating some similarity of the relationships among neural representations of different movements relative to one another during execution and observation. We also found that during action execution, mirror neurons showed consistent patterns of co-modulation both within and between sessions, but other non-mirror neurons that were modulated only during action execution and not during observation showed considerable variability of co-modulation.
Developing forebrain synapses are uniquely vulnerable to sleep loss
Authors: Gay Sean M. , Chartampila Elissavet , Lord Julia S. , Grizzard Sawyer , Maisashvili Tekla , Ye Michael , Barker Natalie K. , Mordant Angie L. , Mills C. Allie , Herring Laura E. , Diering Graham H. 
Published: November 2023

AbstractSleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function and a locus of dysfunction in response to sleep deprivation (SD). Synapse density is highly dynamic during development, becoming stabilized with maturation to adulthood, suggesting sleep exerts distinct synaptic functions between development and adulthood. Importantly, problems with sleep are common in neurodevelopmental disorders including autism spectrum disorder (ASD). Moreover, early life sleep disruption in animal models causes long lasting changes in adult behavior. Different plasticity engaged during sleep necessarily implies that developing and adult synapses will show differential vulnerability to SD. To investigate distinct sleep functions and mechanisms of vulnerability to SD across development, we systematically examined the behavioral and molecular responses to acute SD between juvenile (P21-28), adolescent (P42-49) and adult (P70-100) mice of both sexes. Compared to adults, juveniles lack robust adaptations to SD, precipitating cognitive deficits in the novel object recognition test. Subcellular fractionation, combined with proteome and phosphoproteome analysis revealed the developing synapse is profoundly vulnerable to SD, whereas adults exhibit comparative resilience. SD in juveniles, and not older mice, aberrantly drives induction of synapse potentiation, synaptogenesis, and expression of peri-neuronal nets. Our analysis further reveals the developing synapse as a convergent node between vulnerability to SD and ASD genetic risk. Together, our systematic analysis supports a distinct developmental function of sleep and reveals how sleep disruption impacts key aspects of brain development, providing mechanistic insights for ASD susceptibility.Significance StatementSleep is a fundamental pillar of lifelong health. Sleep disruption is commonly associated with neurodevelopmental conditions including autism spectrum disorder (ASD) and schizophrenia. Therefore, understanding the vulnerabilities associated with developmental sleep loss is an essential research question. Here we systemically examine the molecular and behavioral consequence of sleep deprivation (SD) in developing and adult mice. Compared to adults, developing mice show absent or blunted adaptive responses to SD, and heightened sensitivity to SD-induced cognitive deficits. Our molecular analysis indicates sleep plays an important role in key aspects of brain development including synaptogenesis, and that the effects of SD converge on nodes of genetic risk for ASD. This study provides new insights into the role of sleep in healthy brain development.
Histone H1x in mouse ventral hippocampus correlates with, but does not cause behavioral adaptations to stress
Authors: Kim R. Kijoon , Truby Natalie L. , Silva Gabriella M. , Picone Joseph A. , Miller Cary S. , Neve Rachael L. , Cui Xiaohong , Hamilton Peter J. 
Published: November 2023

AbstractPrior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrate that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8–10-week-old male C57BL/6J mice were randomly assigned to stressed and unstressed groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced experimental mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or unstressed mice. In sum, although we confirm vHipp protein levels of H1x correlate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are correlated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.
Structure-based design of small molecule inhibitors of the cagT4SS ATPase Cagα of Helicobacter pylori
Authors: Morin Claire , Verma Vijay Tailor , Arya Tarun , Casu Bastien , Jolicoeur Eric , Ruel Réjean , Marinier Anne , Sygusch Jurgen , Baron Christian 
Published: November 2023

AbstractWe here describe the structure-based design of small molecule inhibitors of the type IV secretion system ofHelicobacter pylori. The secretion system is encoded by the□cag□pathogenicity island, and we chose Cagα, a hexameric ATPase and member of the family of VirB11-like proteins, as target for inhibitor design. We first solved the crystal structure of Cagα in a complex with the previously identified small molecule inhibitor 1G2. The molecule binds at the interface between two Cagα subunits and mutagenesis of the binding site identified Cagα residues F39 and R73 as critical for 1G2 binding. Based on the inhibitor binding site we synthesized 98 small molecule derivates of 1G2 to improve binding of the inhibitor. We used the production of interleukin-8 of gastric cancer cells duringH. pyloriinfection to screen the potency of inhibitors and we identified five molecules (1G2_1313, 1G2_1338, 1G2_2886, 1G2_2889 and 1G2_2902) that have similar or higher potency than 1G2. Differential scanning fluorimetry suggested that these five molecules bind Cagα, and enzyme assays demonstrated that some are more potent ATPase inhibitors than 1G2. Finally, scanning electron microscopy revealed that 1G2 and its derivatives inhibit the assembly of T4SS-determined extracellular pili suggesting a mechanism for their anti-virulence effect.
A Statistical Framework for Analysis of Trial-Level Temporal Dynamics in Fiber Photometry Experiments
Authors: Loewinger Gabriel , Cui Erjia , Lovinger David , Pereira Francisco 
Published: November 2023

AbstractFiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce detection of effects because they condensewithin-trialsignals into summary measures, and discard trial-level information by averagingacross-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects atevery trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yieldsjoint95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework.
Cell lineage analysis with somatic mutations reveals late divergence of neuronal cell types and cortical areas in human cerebral cortex
Authors: Kim Sonia Nan , Viswanadham Vinayak V. , Doan Ryan N. , Dou Yanmei , Bizzotto Sara , Khoshkhoo Sattar , Huang August Yue , Yeh Rebecca , Chhouk Brian , Truong Alex , Chappell Kathleen M. , Beaudin Marc , Barton Alison , Akula Shyam K. , Rento Lariza , Lodato Michael , Ganz Javier , Szeto Ryan A. , Li Pengpeng , Tsai Jessica W. , Hill Robert Sean , Park Peter J. , Walsh Christopher A. 
Published: November 2023

AbstractThe mammalian cerebral cortex shows functional specialization into regions with distinct neuronal compositions, most strikingly in the human brain, but little is known in about how cellular lineages shape cortical regional variation and neuronal cell types during development. Here, we use somatic single nucleotide variants (sSNVs) to map lineages of neuronal sub-types and cortical regions. Early-occurring sSNVs rarely respect Brodmann area (BA) borders, while late-occurring sSNVs mark neuron-generating clones with modest regional restriction, though descendants often dispersed into neighboring BAs. Nevertheless, in visual cortex, BA17 contains 30-70% more sSNVs compared to the neighboring BA18, with clones across the BA17/18 border distributed asymmetrically and thus displaying different cortex-wide dispersion patterns. Moreover, we find that excitatory neuron-generating clones with modest regional restriction consistently share low-mosaic sSNVs with some inhibitory neurons, suggesting significant co-generation of excitatory and some inhibitory neurons in the dorsal cortex. Our analysis reveals human-specific cortical cell lineage patterns, with both regional inhomogeneities in progenitor proliferation and late divergence of excitatory/inhibitory lineages.
Tweek-dependent formation of ER-PM contact sites enables astrocyte phagocytic function and remodeling of neurons
Authors: Kang Yunsik , Jefferson Amanda , Sheehan Amy , La Torre Rachel De , Jay Taylor , Chiao Lucia , Hulegaard Alex , Corty Megan , Baconguis Isabelle , Zhou Zheng , Freeman Marc R. 
Published: November 2023

SummaryNeuronal remodeling generates an enormous amount of cellular debris, which is cleared from the nervous system by glia. At the larva-to-adult transition,Drosophilaastrocytes transform into phagocytes and engulf degenerating larval synapses, axonal and dendritic debris. Here we show Tweek, a member of the bridge-like lipid transfer protein family, is upregulated in astrocytes as they ramp up their phagocytic function early in metamorphosis, and is essential for internalization and degradation of neuronal debris. Tweek forms a bridge between the endoplasmic reticulum (ER) and plasma membrane (PM), and loss of Tweek disrupts ER-PM contact formation and membrane lipid distribution. Patient-identified mutations in the human homolog associated with Alkuraya-Kucinskas syndrome resulted in similar defects in neuronal remodeling, indicating these are loss of function mutations. We propose Tweek helps establish and maintain ER-PM contacts during astrocyte phagocytic function and drives bulk lipid transfer to the plasma membrane for continued efficient internalization and degradation of neuronal debris.
Development of a multi-scanner facility for data acquisition for digital pathology artificial intelligence
Authors: Humphries Matthew P. , Kaye Danny , Stankeviciute Gaby , Halliwell Jacob , Wright Alexander I , Bansal Daljeet , Brettle David , Treanor Darren 
Published: November 2023

AbstractWhole slide imaging (WSI) of pathology glass slides with high-resolution scanners has enabled the large-scale application of artificial intelligence (AI) in pathology, to support the detection and diagnosis of disease, potentially increasing efficiency and accuracy in tissue diagnosis.Despite the promise of AI, it has limitations. “Brittleness” or sensitivity to variation in inputs necessitates that large amounts of data are used for training. AI is often trained on data from different scanners but not usually by replicating the same slide across scanners. The utilisation of multiple WSI instruments to produce digital replicas of the same glass slides will make more comprehensive datasets and may improve the robustness and generalisability of AI algorithms as well as reduce the overall data requirements of AI training.To this end, the National Pathology Imagine Cooperative (NPIC) has built the AI FORGE (FacilitatingOpportunities forRobustGeneralisable dataEmulation), a unique multi-scanner facility embedded in a clinical site in the NHS to (a) compare scanner performance and (b) replicate digital pathology image datasets across WSI systems.The NPIC AI FORGE currently comprises 15 scanners from 9 manufacturers. It can generate approximately 4000 WSI images per day (approximately 7Tb of image data). This paper describes the process followed to plan and build such a facility.