bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD163 and Tim-4 identify resident intestinal macrophages across sub-tissular regions that are spatially regulated by TGF-β
Authors: Prise Ian E. , Jayaraman Vignesh , Kästele Verena , Daw Rufus H. , Wemyss Kelly , Bridgeman Hayley , Tamburrano Sabrina , Strangward Patrick , Chew Christine , Martens Liesbet , Scott Charlotte L. , Guilliams Martin , Adamson Antony D. , Konkel Joanne E. , Shaw Tovah N. , Grainger John R. 
Published: August 2023

AbstractIn bodily organs, macrophages are localised in poorly understood tissular and sub-tissular niches associated with defined macrophage ontogeny and activity. In the intestine, a paradigm is emerging that long-lived macrophages are dominantly present in the muscular layer, while highly monocyte-replenished populations are found in the lamina propria beneath the epithelial barrier. Whether longevity is restricted in such a simplified manner has not been well explored. Moreover, the impact of specific gut-associated factors on long-lived macrophage functionality and niche occupancy is unknown. We generated sc-RNA-Seq data from wild-type andCcr2−/−mice to identify phenotypic features of long-lived macrophage populations in distinct intestinal niches and identified CD163 as a useful marker to distinguish submucosal/muscularis (S/M) from lamina propria (LP) macrophages. Challenging the emerging paradigm, long-lived macrophages, identified by Tim-4 expression, were found in the LP and S/M. Long-lived LP macrophages are restrained in their response to proinflammatory stimulation compared to short-lived populations in the same location, and to the long-lived population within the S/M. Employing a novelTimd4creTgfbr2fl/flmouse line we demonstrate distinct functions of TGF-β on long-lived macrophages in these two compartments. Importantly, inTimd4creTgfbr2fl/flmice, zonation of CD163+macrophages in the S/M was lost, suggesting TGF-β plays an unappreciated role in positioning of macrophages in the tissue. These data highlight the importance of considering ontogeny and niche when assessing the action of key intestinal regulatory signals.
Urban non-point source pollutants cause microbial community homogenization via increasing deterministic processes
Authors: Li Haizhou , Fan Xiangyu , He Zhiwei , Fu Jing , Wang Yuekai , Yu Jinchen , Yang Shanshan , Wu Jiawang , Wu Li , Zhou Jin 
Published: August 2023

AbstractUrbanization significantly impacts the community structure of aquatic organisms and poses a major threat to river biodiversity. However, the extent to which urbanization is linked to the homogenization of microbial communities and the underlying mechanisms remains poorly understood. In this study, we investigated the bacterial and archaeal communities from cities and neighboring natural rivers across river network located in the Qinling Mountains, Northwest China, and further investigated the alpha and beta diversity patterns and the mechanisms influenced by urbanization. We found that the influx of urban non-point source pollutants created a eutrophic condition, and enhanced the urban river microbial populations. Meanwhile, the rapid urbanization tends to decrease the overall habitat heterogeneity, and imposed stronger homogeneous selection and caused microbial communities biotic homogenization. The mechanisms of biotic homogenization can be attributed to modulating generalist/specialist species and invasion of nonnative species. For instance, the urban river had a greater proportion of fast-growing bacteria, algae, nitrifiers, PAH-degrading bacteria, pathogens, fecal bacteria and antibiotic-resistant bacteria than natural river ecosystems. Overall, urbanization leads to a more uniform river biosphere, causing the extinction of unique local species and a subsequent decrease in the regional species pool.
Morphodynamics of human early brain organoid development
Authors: Jain Akanksha , Gut Gilles , Sanchis-Calleja Fátima , Okamoto Ryoko , Streib Simon , He Zhisong , Zenk Fides , Santel Malgorzata , Seimiya Makiko , Holtackers René , Jansen Sophie Martina Johanna , Camp J. Gray , Treutlein Barbara 
Published: August 2023

AbstractBrain organoids enable the mechanistic study of human brain development, and provide opportunities to explore self-organization in unconstrained developmental systems. Here, we establish long-term, live light sheet microscopy on unguided brain organoids generated from fluorescently labeled human induced pluripotent stem cells, which enables tracking of tissue morphology, cell behaviors, and subcellular features over weeks of organoid development. We provide a novel dual-channel, multi-mosaic and multi-protein labeling strategy combined with a computational demultiplexing approach to enable simultaneous quantification of distinct subcellular features during organoid development. We track Actin, Tubulin, plasma membrane, nucleus, and nuclear envelope dynamics, and quantify cell morphometric and alignment changes during tissue state transitions including neuroepithelial induction, maturation, lumenization, and brain regionalization. Based on imaging and single-cell transcriptome modalities, we find that lumenal expansion and cell morphotype composition within the developing neuroepithelium are associated with modulation of gene expression programs involving extracellular matrix (ECM) pathway regulators and mechanosensing. We show that an extrinsically provided matrix enhances lumen expansion as well as telencephalon formation, and unguided organoids grown in the absence of an extrinsic matrix have altered morphologies with increased neural crest and caudalized tissue identity. Matrixinduced regional guidance and lumen morphogenesis are linked to the WNT and Hippo (YAP1) signaling pathways, including spatially restricted induction of the Wnt Ligand Secretion Mediator (WLS) that marks the earliest emergence of nontelencephalic brain regions. Altogether, our work provides a new inroad into studying human brain morphodynamics, and supports a view that matrix-linked mechanosensing dynamics play a central role during brain regionalization.
Winner-take-all fails to account for pop out accuracy
Authors: Hendler Ori , Segev Ronen , Shamir Maoz 
Published: August 2023

AbstractVisual search involves active scanning of the environment to locate objects of interest against a background of irrelevant distractors. One widely accepted theory posits that pop out visual search is computed by a winner-take-all (WTA) competition between contextually modulated cells that form a saliency map. However, previous studies have shown that the ability of WTA mechanisms to accumulate information from large populations of neurons is limited, thus raising the question of whether WTA can underlie pop out visual search. To address this question, we conducted a modeling study to investigate how accurately the WTA mechanism can detect the deviant stimulus in a pop out task. We analyzed two architectures of WTA networks: single-best-cell WTA, where the decision is made based on a single winning cell, and a generalized population-based WTA, where the decision is based on the winning population of similarly tuned cells. Our results show that WTA performance cannot account for the high accuracy found in behavioral experiments. On the one hand, inherent neuronal heterogeneity prevents the single-best-cell WTA from accumulating information even from large populations. On the other, the accuracy of the generalized population-based WTA algorithm is negatively affected by the widely reported noise correlations. These findings suggest the need for revisiting current understandings of the underlying mechanism of pop out visual search put forward to account for observed behavior.
Regional Differences in Progenitor Consumption Dynamics Shape Brain Growth during Development
Authors: Baumann Natalia , Wagener Robin , Javed Awais , Abe Philipp , Lopes Andrea , Lavalley Adrien , Fuciec Daniel , Magrinelli Elia , Fièvre Sabine , Jabaudon Denis 
Published: August 2023

SUMMARYDeveloping mammalian brains are characterized by disproportionate growth of the forebrain compared to other regions. How this localized expansion occurs is, however, largely unknown. To address this, we identified region-specific neurogenic patterns by creating a single-cell-resolution birthdate atlas of the mouse brain (https://www.neurobirth.org). We report that in forebrain regions, neurogenesis is sustained compared to the hindbrain, where neurogenesis is transient and limited to early brain development. Sustained forebrain neurogenesis reflects lengthened cell cycle and reduced consumptive divisions of ventricular zone progenitors, resulting in a preserved germinal cell pool. Using single-cell RNA sequencing, we identify functional molecular programs of ventricular zone progenitors that spatially and temporally regulate progenitor cycling properties, including through loss-of-function of the forebrain-enriched mitochondrial membrane protein Fam210b. These results reveal a parsimonious mechanism to locally regulate neuronal production, in which the time window during which progenitors generate cells is a critical determinant of region-specific brain expansion.
Just a phase? Causal probing reveals spurious phasic dependence of sensory perception
Authors: Vinao-Carl M. , Gal-Shohet Y. , Rhodes E. , Li J. , Hampshire A. , Sharp D. , Grossman N. 
Published: August 2023

ABSTRACTFor over a decade, electrophysiological studies have reported correlations between sensory perception and the phase of spontaneous pre-stimulus brain oscillations. To date, these findings have been interpreted as evidence that the brain uses neural oscillations to sample and predict upcoming stimuli. Yet, evidence from simulations have shown that analysis artefacts could also lead to spurious pre-stimulus oscillations that appear to predict future brain responses. To address this discrepancy, we conducted an experiment in which visual stimuli were presented timed to specific phases of spontaneous alpha and theta oscillations. This allowed us to causally probe the role of ongoing neural activity in visual processing independent of the stimulus-evoked dynamics. Our findings did not support a causal link between spontaneous alpha / theta rhythms and behaviour. However, spurious correlations between theta phase and behaviour emerged offline using gold-standard acausal time-frequency analyses. These findings demonstrate that care should be taken when inferring causal relationships between neural activity and behaviour using acausal analyses.HIGHLIGHTSWe causally probed the role of spontaneous EEG rhythms in visual attention via phase-locking.Theta phase predicted behaviour offline, but cues presented in real-time with theta had no effect on behaviour.Spurious theta rhythmic sampling is an artefact of the evoked potential and acausal filtering.ecHT accurately computes the phase in real-time and mitigates erroneous phase-behaviour correlations.
Phosphorylation-controlled cohesion of a nuclear condensate regulates mRNA retention
Authors: McIntyre Alexa B. R. , Tschan Adrian Beat , Meyer Katrina , Walser Severin , Rai Arpan Kumar , Fujita Keisuke , Pelkmans Lucas 
Published: August 2023

AbstractNuclear speckles are membraneless organelles that associate with active transcription sites and participate in post-transcriptional mRNA processing. During the cell cycle, nuclear speckles dissolve following phosphorylation of their protein components. Here, we identify the PP1 family as the phosphatases that counteract kinase-mediated dissolution. PP1 overexpression increases speckle cohesion and leads to retention of polyadenylated RNA within speckles and the nucleus. Using APEX2 proximity labeling combined with RNA-sequencing, we characterized the relationship between the cohesion of nuclear speckles and the recruitment of specific RNAs. We find that many transcripts are preferentially enriched within nuclear speckles compared to the nucleoplasm, particularly chromatin- and nucleus-associated transcripts. While total polyadenylated RNA retention increased with nuclear speckle cohesion, the ratios of most mRNA species to each other were constant, indicating non-selective, or proportional, retention. We then explored whether nuclear speckle cohesion changes in response to environmental perturbations associated with changes in kinase or phosphatase activity. We found that cellular responses to heat shock, oxidative stress, and hypoxia include changes to the cohesion of nuclear speckles and mRNA retention. Our results demonstrate that tuning the material properties of nuclear speckles provides a mechanism for the acute control of mRNA localization.
Belief embodiment through eye movements facilitates memory-guided navigation
Authors: Stavropoulos Akis , Lakshminarasimhan Kaushik J. , Angelaki Dora E. 
Published: August 2023

AbstractNeural network models optimized for task performance often excel at predicting neural activity but do not explain other properties such as the distributed representation across functionally distinct areas. Distributed representations may arise from animals’ strategies for resource utilization, however, fixation-based paradigms deprive animals of a vital resource: eye movements. During a naturalistic task in which humans use a joystick to steer and catch flashing fireflies in a virtual environment lacking position cues, subjects physically track the latent task variable with their gaze. We show this strategy to be true also during an inertial version of the task in the absence of optic flow and demonstrate that these task-relevant eye movements reflect an embodiment of the subjects’ dynamically evolving internal beliefs about the goal. A neural network model with tuned recurrent connectivity between oculomotor and evidence-integrating frontoparietal circuits accounted for this behavioral strategy. Critically, this model better explained neural data from monkeys’ posterior parietal cortex compared to task-optimized models unconstrained by such an oculomotor-based cognitive strategy. These results highlight the importance of unconstrained movement in working memory computations and establish a functional significance of oculomotor signals for evidence-integration and navigation computations via embodied cognition.
Ocular TRPV1 deficiency protects from dry eye-induced corneal nerve damage
Authors: Pizzano Manuela , Vereertbrugghen Alexia , Cernutto Agostina , Sabbione Florencia , Keitelman Irene A , Shiromizu Carolina M , Aguilar Douglas Vera , Fuentes Federico , Giordano Mirta N , Trevani Analía S , Galletti Jeremías G 
Published: August 2023

AbstractBackgroundCorneal nerve damage causes the most clinically significant symptoms in dry eye disease (DED) yet its pathophysiology remains poorly understood. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro but whether it contributes to corneal neuropathy is unknown. Therefore, here we explored the role of TRPV1 in DED-associated corneal nerve damage.MethodsSurgical DED was induced in TRPV1-deficient (TRPV1KO) and wild-type (wt) mice. Corneal nerve function was measured on days 0, 5, and 10 by mechanical and capsaicin sensitivity and eye-closing ratio as an indicator of non-evoked pain. Nerve and epithelial morphology was evaluated by confocal microscopy of corneal wholemounts. Pharmacological TRPV1 inhibition in wild-type mice was also evaluated.Resultswt and TRPV1KO mice developed comparable ocular desiccation and corneal epithelial damage. Contrasting with wt mice, corneal mechanosensitivity in TRPV1KO mice did not decrease with disease progression. Capsaicin sensitivity increased in wt mice with DED, and consistently, wt but not TRPV1KO mice with DED displayed signs of non-evoked pain. Wt mice with DED exhibited nerve degeneration throughout the corneal epithelium whereas TRPV1KO mice only developed a reduction in the most superficial nerve endings that failed to propagate to the deeper subbasal corneal nerves. Pharmacological blockade of ocular TRPV1 activity reproduced these findings in wt mice with DED. Although TRPV1KO mice with DED had fewer pathogenic Th1 and Th17 CD4+ T cells in the lymph nodes, conjunctival immune infiltration was comparable between strains. Moreover, CD4+ T cells from wt and TRPV1KO mice with DED were equally pathogenic when transferred into T cell-deficient mice, confirming that TRPV1 activity in T cells is not involved in corneal neuropathy.ConclusionsAlthough ocular desiccation is sufficient to trigger superficial corneal nerve damage in DED, proximal propagation of axonal degeneration requires TRPV1 signaling. Conversely, local inflammation sensitizes ocular TRPV1 channels, which are also involved in ocular pain, a key symptom of the disease. Thus, our findings suggest that ocular TRPV1 overactivation is a driving force in DED-associated corneal neuropathy and a potential therapeutic target.Graphical abstract
Cell therapy with IL-10-producing group 2 innate lymphoid cells suppresses Graft-versus-Host disease
Authors: Reid Kyle T. , Colpitts Sarah J. , Mathews Jessica A. , Carreira Abel Santos , Murphy Julia M. , Borovsky Dorota T. , Cui Wenhui , Moya Tommy Alfaro , Sachewsky Nadia , An James , Xia Yubing , Mortha Arthur , Lee Jong Bok , Zhang Li , Novitzky-Basso Igor , Mattsson Jonas , Crome Sarah Q. 
Published: August 2023

AbstractIL-10 producing group 2 innate lymphoid cells (ILC210) have immunoregulatory functions, and limit harmful immune responses across various tissues. Despite their crucial roles in maintaining immune homeostasis, the cell therapy potential of human ILC210has not been demonstrated, due to both limited numbers in human peripheral blood and lack of definitive markers for identification. Here, we isolate and expand circulating human ILC210, and assess their cell therapy potential in a humanized model of Graft-versus-Host Disease (GVHD). Cell therapy with human ILC210decreased GVHD severity and prolonged survival of NOD-scidIL2Rγnull(NSG) mice. Adoptive transfer of ILC210inhibited pathogenic T cell proliferation and intestinal infiltration, and suppressed CD4+Th1 and CD8+Tc1 cells in an IL-4 and IL-10 dependent manner. Critically, increased proportions of ILC2s did not correlate with higher rates of cancer relapse in HSCT recipients, and adoptive transfer of ILC210did not compromise graft-versus-leukemic (GVL) effects in a humanized model. Finally, we identify CD49d and CD86 as novel markers that discriminate ILC210from conventional ILC2s. Collectively, these findings demonstrate the potential of harnessing ILC210in cell therapies for GVHD and other immune-driven pathologies.
DSSP in Gromacs: tool for defining secondary structures of proteins in trajectories
Authors: Gorelov S. V. , Titov A. I. , Tolicheva O.A. , Konevega A. L. , Shvetsov A. V. 
Published: August 2023

AbstractThis work describes a fast implementation of software algorithm associated with determination of protein secondary structure based on the DSSP algorithm. This implementation is fully compatible with the DSSP v.4 algorithm and implemented as native Gromacs trajectory analysis module which allows to analyze molecular dynamics trajectories without any restrictions of the original DSSP implementation. Also this implementation works much faster then original DSSP v.4 algorithm.TOC Graphic
The germline coordinates mitokine signaling
Authors: Shen Koning , Durieux Jenni , Mena Cesar G. , Webster Brant M. , Kimberly Tsui C. , Zhang Hanlin , Joe Lawrence , Berendzen Kristen , Dillin Andrew 
Published: August 2023

AbstractThe ability of mitochondria to coordinate stress responses across tissues is critical for health. InC. elegans, neurons experiencing mitochondrial stress elicit an inter-tissue signaling pathway through the release of mitokine signals, such as serotonin or the WNT ligand EGL-20, which activate the mitochondrial unfolded protein response (UPRMT) in the periphery to promote organismal health and lifespan. We find that germline mitochondria play a surprising role in neuron-to-peripheral UPRMTsignaling. Specifically, we find that germline mitochondria signal downstream of neuronal mitokines, like WNT and serotonin, and upstream of lipid metabolic pathways in the periphery to regulate UPRMTactivation. We also find that the germline tissue itself is essential in UPRMTsignaling. We propose that the germline has a central signaling role in coordinating mitochondrial stress responses across tissues, and germline mitochondria play a defining role in this coordination because of their inherent roles in germline integrity and inter-tissue signaling.
Development and Clinical Evaluation of AlcoChange: a Digital Therapeutic for Patients with Alcohol-Related Liver Disease
Authors: Mehta G , Lin S , Nadar A , Bharadwaj PV , Kumar R , Balaji A , Macdonald S , Sheikh M , Saeidinejad MM , Sharma SR , King JJ , Mookerjee RP , McDonagh L , Afuwape SA , Moore K , Jalan R 
Published: August 2023

AbstractBackground and aimsMaintenance of abstinence in alcohol-related liver disease (ARLD) is a major unmet therapeutic need. Digital therapeutics can deliver ongoing behavioural therapy, in real-time, for chronic conditions. The aim of this project was to develop and clinically test AlcoChange, a novel digital therapeutic for ARLD.MethodsAlcoChange was developed using validated behaviour change techniques (BCTs) and a digital alcohol breathalyser. This was an open-label, single-centre study. Patients with ARLD, ongoing alcohol use (within 1 month) and possession of a suitable smartphone were eligible. Patients were recruited from inpatient and outpatient settings, and received AlcoChange therapy for 3-months. The primary outcome was reduction in alcohol use from baseline to 3-months, measured by timeline follow-back (TLFB). Secondary outcomes included: (i) compliance with the AlcoChange app, (ii) alcohol-related and all-cause hospital re-admissions up to 1-year, (iii) qualitative analysis to determine factors associated with compliance.ResultsSixty-five patients were recruited, of whom forty-one completed the study per-protocol. Patients compliant with the intervention (>60 logins over 3-months) had a significant reduction in alcohol use from baseline compared to non-compliant patients [median (IQR): −100% (100% to −55.1%)vs−57.1% (−95.3% to +32.13%), p=0.029]. The proportion attaining abstinence at 3-months was higher in the compliant group (57.1%vs22.2%, p=0.025). The compliant group had a significantly decreased risk of subsequent alcohol-related re-admission up to 12-months (p=0.008). Qualitative analysis demonstrated receiving in-app feedback and presence of health-related ‘sentinel event’ were predictors of compliance with the intervention.ConclusionsUse of the novel digital therapeutic, AlcoChange, was associated with a significant reduction in alcohol use and increase in proportion attaining abstinence in ARLD patients. Definitive, randomized trials are warranted for this intervention.