bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinal motoneuron excitability is homeostatically-regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice
Authors: Antonucci Stefano , Caron Guillaume , Dikwella Natalie , Krishnamurty Sruthi Sankari , Harster Anthony , Zarrin Hina , Tahanis Aboud , Heuvel Florian olde , Danner Simon M. , Ludolph Albert C. , Grycz Kamil , Bączyk Marcin , Zytnicki Daniel , Roselli Francesco 
Published: March 2024

AbstractHomeostatic feedback loops are essential to stabilize the activity of neurons and neuronal networks. It has been hypothesized that, in the context of Amyotrophic Lateral Sclerosis (ALS), an excessive gain in feedback loops might hyper- or hypo-excite motoneurons (MNs) and contribute to the pathogenesis. Here, we investigated how the neuromodulation of MN intrinsic properties is homeostatically controlled in presymptomatic adult SOD1(G93A) mice and in the age-matched control WT mice. First, we determined that β2 and β3-adrenergic receptors, which are Gs-coupled receptors and subject to tight and robust feedback loops, are specifically expressed in spinal MNs of both SOD1 and WT mice at P45. We then demonstrated that these receptors elicit a so-far overlooked neuromodulation of the firing and excitability properties of MNs. These electrical properties are homeostatically regulated following receptor engagement, which triggers ion channel transcriptional changes and downregulates those receptors. These homeostatic feedbacks are not dysregulated in presymptomatic SOD1 mice, and they set the MN excitability upon β-adrenergic neuromodulation.
Associations between parenting and cognitive and language abilities at age 2 depend on prenatal exposure to disadvantage
Authors: Leverett Shelby D. , Brady Rebecca G. , Tooley Ursula A. , Lean Rachel E. , Tillman Rebecca , Wilson Jillian , Ruscitti Michayla , Triplett Regina L. , Alexopoulos Dimitrios , Gerstein Emily D. , Smyser Tara A. , Warner Barbara , Luby Joan L. , Smyser Christopher D. , Rogers Cynthia E. , Barch Deanna M. 
Published: March 2024

AbstractObjectiveTo investigate whether parenting and/or neonatal brain volumes mediate the associations between prenatal social disadvantage (PSD) and cognitive/language abilities; and whether these mechanisms vary by level of disadvantage.Study DesignPregnant women were recruited from obstetric clinics in St Louis, Missouri. PSD encompassed access to social (e.g., education) and material (e.g., income-to-needs, health insurance, area deprivation, and nutrition) resources during pregnancy. Neonates underwent brain magnetic resonance imaging. Mother-child dyads (N=202) returned at age 1 for parenting measures and at age 2 for cognition/language assessments (Bayley-III). Generalized additive and mediation models tested hypotheses.ResultsGreater PSD was nonlinearly associated with poorer cognitive/language scores. The relation between parenting and cognition/language was moderated by PSD, such that supportive and non-supportive parenting behaviors only related to cognition/language in children with low PSD. Further, parenting mediations differed by level of PSD, such that both supportive and non-supportive parenting mediated PSD-cognition/language associations in children with low PSD, but not in children with high PSD. PSD-associated reductions in neonatal subcortical grey matter (β=.19,q=.03), white matter (β=.23,q=.02), and total brain volume (β=.18,q=.03) were associated with lower cognition, but they did not mediate PSD-cognition associations.ConclusionsParenting moderates and mediates associations between PSD and early cognitive and language development, but only in families with lower levels of social disadvantage. These findings, while correlational, suggest that there may be a critical threshold of disadvantage, below which mediating or moderating factors become less effective, highlighting the importance of reducing disadvantage as primary prevention.
Expert Navigators Deploy Rational Complexity-Based Decision Precaching for Large-Scale Real-World Planning
Authors: Fernandez Velasco Pablo , Griesbauer Eva-Maria , Brunec Iva , Morley Jeremy , Manley Ed , McNamee Daniel C. , Spiers Hugo J. 
Published: March 2024

AbstractEfficient planning is a distinctive hallmark of intelligence in humans, who routinely make rapid inferences over complex world contexts. However, studies investigating how humans accomplish this tend to focus on naive participants engaged in simplistic tasks with small state-spaces, which do not reflect the intricacy, ecological validity, and human specialisation in real-world planning. In this study, we examine the street-by-street route planning of London taxi drivers navigating across more than 26,000 streets in London (UK). We explore how planning unfolded dynamically over different phases of journey construction and identify theoretic principles by which these expert human planners rationally precache decisions at prioritised environment states in an early phase of the planning process. In particular, we find that measures of path complexity predict human mental sampling prioritisation dynamics independent of alternative measures derived from the real spatial context being navigated. Our data provide real-world evidence for complexity-driven remote state access within internal models and precaching during human expert route planning in very large structured spaces.Significance statementHumans can plan efficiently in incredibly complex situations. Existing work has looked at naive participants in simple tasks, which might not be representative of how experts plan in the real world. Here, we study the real-world planning process of London taxi drivers – famous for their expert knowledge of London. By analyzing their response times as a proxy for thinking times, we reveal that at an early stage in their thought process, they store decisions at key street junctions to keep them in mind for later planning. Using computational modeling, we show that taxi drivers prioritize inference at street junctions according to normative metrics measuring how critical a particular decision is for reducing the complexity of planning across the entire city.
Regenerative human liver organoids (HLOs) in a pillar/perfusion plate for hepatotoxicity assays
Authors: Shrestha Sunil , Acharya Prabha , Kang Soo-Yeon , Vanga Manav Goud , Reddy Lekkala Vinod Kumar , Liu Jiafeng , Yang Yong , Joshi Pranav , Lee Moo-Yeal 
Published: March 2024

AbstractHuman liver organoids (HLOs) differentiated from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells (ASCs) can recapitulate the structure and function of human fetal liver tissues, thus being considered as a promising tissue model for liver diseases and predictive compound screening. However, the adoption of HLOs in drug discovery faces several technical challenges, which include the lengthy differentiation process with multiple culture media leading to batch-to-batch variation, short-term maintenance of hepatic functions post-maturation, low assay throughput due to Matrigel dissociation and HLO transfer to a microtiter well plate, and insufficient maturity levels compared to primary hepatocytes. To address these issues, expandable HLOs (Exp-HLOs) derived from human iPSCs were generated by optimizing differentiation protocols, which were rapidly printed on a 144-pillar plate with sidewalls and slits (144PillarPlate) and dynamically cultured for up to 20 days into differentiated HLOs (Diff-HLOs) in a 144-perfusion plate with perfusion wells and reservoirs (144PerfusionPlate) forin situorganoid culture and analysis. The dynamically cultured Diff-HLOs exhibited greater maturity and reproducibility than those cultured statically, especially after a 10-day differentiation period. In addition, Diff-HLOs in the pillar/perfusion plate were tested with acetaminophen and troglitazone for 3 days to assess drug-induced liver injury (DILI) and then incubated in an expansion medium for 10 days to evaluate liver recovery from DILI. The assessment of liver regeneration post-injury is critical to understanding the mechanism of recovery and determining the threshold drug concentration beyond which there will be a sharp decrease in the liver’s regenerative capacity. We envision that bioprinted Diff-HLOs in the pillar/perfusion plate could be used for high-throughput screening (HTS) of hepatotoxic compounds due to the short-term differentiation of passage-able Exp-HLOs, stable hepatic function post-maturation, high reproducibility, and high throughput with capability ofin situorganoid culture, testing, staining, imaging, and analysis.Graphical abstractThe overall process of dynamic liver organoid culture andin situanalysis in the 144PillarPlate/144PerfusionPlate for high-throughput hepatotoxicity assays.
Functional-based parcellation of the mouse prefrontal cortex for network perturbation analysis
Authors: Savvateev Iurii , Grimm Christina , Markicevic Marija , Grandjean Joanes , Wenderoth Nicole , Polania Rafael , Zerbi Valerio 
Published: March 2024

AbstractThe prefrontal cortex (PFC) is a region of the brain involved in higher-order cognitive processes such as attention, emotional regulation, and social behavior, making it a hotspot for an ongoing clinical and fundamental research. Importantly, its functionality is intricately interconnected within a wide array of functional networks encompassing multiple other brain areas. However, the delineation of distinct subdivisions within the mouse PFC and their contributions to the broader brain network function remain topics of ongoing debate. In the current study, we used resting-state functional magnetic resonance imaging (rsfMRI) from a large cohort of wildtype animals to derive the functional-connectivity (FC) based parcellation of the mouse PFC with voxel resolution. Our findings indicate the presence of FC-based clusters that deviate from the established anatomical subdivisions within the cingulate and prelimbic areas, while they align in infralimbic and orbital cortices. To further underscore the association of these FC-based clusters with distinct functional networks, we performed network-specific perturbations using chemogenetics in the identified clusters in dorsal PFC and monitor the elicited effects with fMRI (chemo-fMRI). Our recordings revealed that FC perturbations were observed only within the functional networks linked to the targeted clusters and did not spread to neighbouring anatomical areas or functional clusters. We propose that FC-based parcellation is a valuable approach for tracking the impact of external activations and confirming the precise site of activation.Abstract Figure
Integrating Optogenetic Stimulation of Olfactory Bulb Glomeruli with Foot Shock Fear Conditioning: A Robust Method for Investigating Olfactory-based Fear Conditioning
Authors: Kuruppath Praveen 
Published: March 2024

AbstractThe integration of optogenetic techniques with traditional behavioral paradigms has provided novel insights into the neural mechanisms underlying olfactory-based fear conditioning. Olfactory cues are potent triggers for fear responses, and understanding the intricate neural dynamics involved in olfactory fear learning is crucial for unraveling the complexities of aversive memory formation. In this study, a robust method is presented that combines optogenetic stimulation of olfactory bulb glomeruli with foot shock fear conditioning to investigate olfactory-based fear learning in mice. By merging optogenetic manipulation with behavioral assays, a comprehensive framework for studying the mechanisms of olfactory fear conditioning is provided. This method offers new avenues for exploring the neural dynamics of adaptive responses to olfactory threats and may have implications for understanding fear-related disorders.
Comparative framework and adaptation of ACME HS approach to single cell isolation from fresh-frozen endocrine tissues
Authors: Utkina Marina , Shcherbakova Anastasia , Deviatiiarov Ruslan , Ryabova Alina , Loguinova Marina , Trofimov Valentin , Kuznetsova Anna , Petropavlovskiy Mikhail , Salimkhanov Rustam , Maksimov Denis , Albert Eugene , Golubeva Alexandra , Asaad Walaa , Urusova Lilia , Bondarenko Ekaterina , Lapshina Anastasia , Shutova Alexandra , Beltsevich Dmitry , Gusev Oleg , Dzeranova Larisa , Melnichenko Galina , Minniakhmetov Ildar , Dedov Ivan , Mokrysheva Natalya , Popov Sergey 
Published: March 2024

AbstractCurrent scRNA-seq studies of solid tissues mostly rely on enzymatic dissociation of fresh samples or the fallback on nuclei isolation from frozen or partially fixed samples. However, due to the complex tissue organization or cell fragility, it could be challenging to apply these approaches to the sensitive endocrine tissues. That is, dissociating intact cells from such problematic fresh-frozen samples routinely collected by biobanks remains challenging.In this study, we adapted the acetic-methanol dissociation method – ACME High Salt (ACME HS) to effectively isolate intact single cells from fresh-frozen endocrine tumor samples, including adrenal gland neoplasms, thyroid carcinomas, and pituitary neuroendocrine tumors. We compared the ability of enzymatic, ACME HS, and nuclear isolation methods to preserve the integrity of major cell types and gene expression across 41 tissue samples of different origins. We demonstrated that ACME HS simultaneously dissociates and fixes cells, thus preserving morphology and a high RNA integrity number in problematic cell types. This finding renders the ACME HS dissociation method a valuable alternative in scRNA-seq protocols for challenging tissues where obtaining live cell suspension is difficult or impossible.
Volume Electron Microscopy Analysis of Synapses in Associative and Primary Regions of the Human Cerebral Cortex
Authors: Cano-Astorga Nicolás , Plaza-Alonso Sergio , DeFelipe Javier , Alonso-Nanclares Lidia 
Published: March 2024

AbstractFunctional and structural studies investigating macroscopic connectivity in the human cerebral cortex suggest that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored due to the difficulties involved in studying the human brain at the nanoscopic level. In the present work, we conducted volume electron microscopy to investigate the synaptic organization of the human brain obtained at autopsy. Specifically, we examined layer III of Brodmann areas 17, 3b, and 4, as representative areas of primary visual, somatosensorial, and motor cortex. Additionally, we conducted comparative analyses with our previous synaptic datasets of layer III from temporopolar and anterior cingulate associative cortical regions (Brodmann areas 24, 38, and 21). 9,690 synaptic junctions were 3D reconstructed, showing that certain synaptic characteristics appeared to be specific to particular cortical regions. The number of synapses per volume, the proportion of the postsynaptic targets, and the synaptic size may distinguish one region from another, regardless of whether they are associative or primary cortex. By contrast, other synaptic characteristics were common to all analyzed regions, such as the proportion of excitatory and inhibitory synapses, their shapes, their spatial distribution, and a higher proportion of synapses located on dendritic spines. These observations may be included within the general rules of synaptic organization of the human cerebral cortex. The present results on nanoscopic characteristics of synapses provide further insights into the structural design of the human cerebral cortex.Significance statementStructural and functional studies investigating macroscopic connectivity in the human cerebral cortex have suggested that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored. Here, thousands of synaptic junctions were 3D reconstructed in associative and primary cortical regions. We found that certain synaptic characteristics appeared to be specific to particular cortical regions —regardless of whether they are associative or primary cortex— whereas others were common to all analyzed regions. The present results provide further insights into the structural design of the human cerebral cortex.
Anabolic lipid metabolism regulates adipose type 2 innate lymphoid cell differentiation to maintain metabolic health
Authors: Theodorou Maria Rafailia , Yu Jiangyan , Nikolka Fabian , Zurkovic Jelena , Wientjens Chantal , Weiss Patricia , Rombo Roman , Karagiannis Fotios , Thiele Christoph , Hasenauer Jan , Hiller Karsten , Wilhelm Christoph 
Published: March 2024

SummaryGroup 2 innate lymphoid cells (ILC2) residing in the adipose tissue play an important role in maintaining the metabolic health and energy balance of the organisms. In obesity ILC2 numbers are reduced and their function is impaired, leading to the progression of metabolic inflammation. However, which events impact on ILC2 biology in the adipose tissue in obesity remains unresolved. Here, we find that high fat diet (HFD)-induced obesity in mice results in the metabolic reprogramming of adipose ILC2, impairing mitochondrial function and the expression of the enzyme Acetyl-CoA carboxylase 1 (ACC1). Investigating a possible connection between ACC1 and obesity-induced changes in ILC2, we show that fatty acids directly reduce the expression of ACC1, while pharmacological inhibition of ACC1 diminishes mitochondrial function and ILC2 metabolism. Furthermore, deletion of ACC1 in ILC2 phenocopies the overall reduction and functional impairment of ILC2 observed in obesity, which ultimately leads to increased triglycerides in circulation, adipose tissue hypertrophy and inflammation, even in the absence of HFD. Through single-cell RNA sequencing analysis we uncover that HFD-feeding or deletion of ACC1 results in the accumulation of undifferentiated ILC2 and ILC progenitors in the adipose tissue, suggesting that ACC1 may primarily regulate the maturation of ILC2. Together, these results reveal that obesity could predominately impair adipose ILC2 differentiation and activation by impacting on the expression of ACC1, rather than inducing cell death through lipid overload and lipotoxicity.
Plasma cell heterogeneity is driven by type of immune challenge
Authors: Khamyath Mélanie , Lereclus Emilie , Gourhand Vanessa , Debureaux Pierre-Edouard , Moulin Clémentine , Gary Hélène , Bachelerie Françoise , Balabanian Karl , Espéli Marion , Bonaud Amélie 
Published: March 2024

AbstractPlasma cells play an essential role in humoral immunity, but many questions remain regarding the heterogeneity of this population, both in terms of ontogeny and involvement in the immune response. In this work, we have identified 5 subsets of plasma cells in human and mouse lymphoid tissues. These subpopulations were distinguished by differential expression of CD62L, CXCR4, FcγRIIb and CD93. The antigenic context as well as the B cell of origin directed plasma cell differentiation towards specific subtypes that display distinct migratory and survival abilitiesin vivo. Altogether, ours results unveil that plasma cell phenotypic and functional heterogeneity relies on intrinsic imprinting during B cell activation.
Model-based frequency-and-phase correction of1H MRS data with 2D linear-combination modeling
Authors: Simicic Dunja , Zöllner Helge J. , Davies-Jenkins Christopher W. , Hupfeld Kathleen E. , Edden Richard A. E. , Oeltzschner Georg 
Published: March 2024

AbstractPurposeRetrospective frequency-and-phase correction (FPC) methods attempt to remove frequency- and-phase variations between transients to improve the quality of the averaged MR spectrum. However, traditional FPC methods like spectral registration struggle at low SNR. Here, we propose a method that directly integrates FPC into a two-dimensional linear-combination model (2D-LCM) of individual transients (‘model-based FPC’). We investigated how model-based FPC performs compared to the traditional approach, i.e., spectral registration followed by 1D-LCM in estimating frequency-and-phase drifts and, consequentially, metabolite level estimates.MethodsWe created synthetic in-vivo-like 64-transient short-TE sLASER datasets with 100 noise realizations at 5 SNR levels and added randomly sampled frequency and phase variations. We then used this synthetic dataset to compare the performance of 2D-LCM with the traditional approach (spectral registration, averaging, then 1D-LCM). Outcome measures were the frequency/phase/amplitude errors, the standard deviation of those ground-truth errors, and amplitude Cramér Rao Lower Bounds (CRLBs). We further tested the proposed method on publicly available in-vivo short-TE PRESS data.Results2D-LCM estimates (and accounts for) frequency-and-phase variations directly from uncorrected data with equivalent or better fidelity than the conventional approach. Furthermore, 2D-LCM metabolite amplitude estimates were at least as accurate, precise, and certain as the conventionally derived estimates. 2D-LCM estimation of frequency and phase correction and amplitudes performed substantially better at low-to-very-low SNR.ConclusionModel-based FPC with 2D linear-combination modeling is feasible and has great potential to improve metabolite level estimation for conventional and dynamic MRS data, especially for low-SNR conditions, e.g., long TEs or strong diffusion weighting.
Real-time transcriptomic profiling in distinct experimental conditions
Authors: Butto Tamer , Pastore Stefan , Müller Max , Iyer Kaushik Viswanathan , Mündnich Stefan , Wierczeiko Anna , Friedland Kristina , Helm Mark , Winz Marie-Luise , Gerber Susanne 
Published: March 2024

AbstractNanopore technology offers real-time sequencing opportunities, providing rapid access to sequenced data and allowing researchers to manage the sequencing process efficiently, resulting in cost-effective strategies. Here, we present focused case studies demonstrating the versatility of real-time transcriptomics analysis in rapid quality control for long-read RNA-seq. We illustrate its utility through three experimental setups: 1) transcriptome profiling of distinct human cellular populations, 2) identification of experimentally enriched transcripts, and 3) identification of experimentally manipulated genes (knockout and overexpression) in several yeast strains. We show how to perform multiple layers of quality control as soon as sequencing has started, addressing both the quality of the experimental and sequencing traits. Real-time quality control measures assess sample/condition variability and determine the number of identified genes per sample/condition. Furthermore, real-time differential gene/transcript expression analysis can be conducted at various time points post-sequencing initiation (PSI), revealing dynamic changes in gene/transcript expression between two conditions. Using real-time analysis, which occurs in parallel to the sequencing run, we identified differentially expressed genes/transcripts as early as 1-hour PSI. These changes were consistently observed throughout the entire sequencing process. We discuss the new possibilities offered by real-time data analysis, which have the potential to serve as a valuable tool for rapid and cost-effective quality checks in specific experimental settings and can be potentially integrated into clinical applications in the future.