bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti- and pro-inflammatory milieu differentially regulate differentiation and immune functions of oligodendrocyte progenitor cells
Authors: Zveik Omri , Rechtman Ariel , Brill Livnat , Vaknin-Dembinsky Adi 
Published: November 2023

AbstractOligodendrocyte progenitor cells (OPC) were regarded for years solely for their regenerative role; however, their immune-modulatory roles have gained much attention recently, particularly in the context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating the interactions between their intrinsic regenerative and immune functions, as well as their relationship with the inflamed central nervous system (CNS) environment, a key factor in MS pathology. We examined the effects of pro-inflammatory cytokines, represented by interferon (IFN)-γ and tumor necrosis factor (TNF)-α, as well as anti-inflammatory cytokines, represented by interleukin(IL)-4 and IL-10, on OPC differentiation and immune characteristics. Using primary cultures, ELISA, and immunofluorescence stainings, we assessed differentiation capacity, phagocytic activity, major histocompatibility complex (MHC)-II expression, and cytokine secretion. We observed that the anti-inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF-α led to intact differentiation, increased phagocytic activity, high levels of MHC-II expression, and cytokines secretion. Those effects were attributed to signaling via TNF-receptor-2 (TNFR2) and counteracted the detrimental effects of IFNγ on OPC differentiation. Our findings suggest that a pro-regenerative, permissive inflammatory environment is needed for OPCs to execute both regenerative and immune-modulatory functions.
Drivers of population dynamics of at-risk populations change with pathogen arrival
Authors: Grimaudo Alexander T. , Hoyt Joseph R. , King R. Andrew , Toomey Rickard S. , Simpson Chris , Holliday Cory , Silvis Alexander , Doyle Rick T. , Kath Joseph A. , Armstrong Mike P. , Brack Virgil , Reynolds Richard J. , Williamson Ryan H. , Turner Gregory G. , Kuczynska Vona , Meyer Jordan J. , Jansky Kyle , Herzog Carl J. , Hopkins Skylar R. , Langwig Kate E. 
Published: November 2023

AbstractSuccessful wildlife conservation in an era of rapid global change requires understanding determinants of species population abundance and growth. However, when populations are faced with novel stressors, factors associated with healthy and growing populations can change, necessitating a shift in conservation strategies. For example, emerging infectious diseases can cause conditions previously beneficial or neutral to host populations to increase disease impacts. Here, we paired a population dataset of 265 colonies of the federally endangered Indiana bat (Myotis sodalis) with 50.7 logger-years of environmental data to explore factors that affected colony response to white-nose syndrome (WNS), an emerging fungal disease. We found wide variation in colony responses to WNS, ranging from extirpation to stabilization and persistence. Simulating future population dynamics suggests that most extirpations have already occurred, as the pathogen has been present for several years in most colonies, and that small colonies were more susceptible to extirpation than large ones. Further, while temperature and humidity conditions of hibernacula appeared unassociated with Indiana bat colony growth prior to WNS, extirpation risk following pathogen arrival was elevated in colonies that used colder and wetter hibernacula. Additionally, rates of decline were greater in colder hibernacula, opposite the association for a sympatric bat species. Overall, this study illustrates that emerging infectious diseases can change the factors associated with host population abundance and optimal growth, including through novel environmental associations, which can vary across host species. Consideration of these shifting associations and intrinsic differences between impacted host species will be essential to successful species conservation.
Loss of Myeloid Cell-Specific β2-Adrenergic Receptor Expression Ameliorates Cardiac Function and Remodeling after Acute Ischemia
Authors: Nayak Tapas K. , Bajpai Anamika , Patwa Viren , Carter Rhonda L. , Enjamuri Nitya , Gao Erhe , Xiang Yang K. , Tilley Douglas G. 
Published: November 2023

AbstractMyeloid cells, including neutrophils, monocytes and macrophages, accumulate quickly after ischemic injury in the heart where they play integral roles in the regulation of inflammation and repair. We previously reported that deletion of β2-adrenergic receptor (β2AR) in all cells of hematopoietic origin resulted in generalized disruption of immune cell responsiveness to injury, but with unknown impact on myeloid cells specifically. To investigate this, we crossed floxed β2AR (F/F) mice with myeloid cell-expressing Cre (LysM-Cre) mice to generate myeloid cell-specific β2AR knockout mice (LB2) and subjected them to myocardial infarction (MI). Via echocardiography and immunohistochemical analyses, LB2 mice displayed better cardiac function and less fibrotic remodeling after MI than the control lines. Despite similar accumulation of myeloid cell subsets in the heart at 1-day post-MI, LB2 mice displayed reduced numbers of Nu by 4 days post-MI, suggesting LB2 hearts have enhanced capacity for Nu efferocytosis. Indeed, bone marrow-derived macrophage (BMDM)-mediated efferocytosis of Nu was enhanced in LB2-versus F/F-derived cells in vitro. Mechanistically, several pro-efferocytosis-related genes were increased in LB2 myeloid cells, with annexin A1 (Anxa1) in particular elevated in several myeloid cell types following MI. Accordingly, shRNA-mediated knockdown ofAnxa1in LB2 bone marrow prior to transplantation into irradiated LB2 mice reduced Mac-induced Nu efferocytosis in vitro and prevented the ameliorative effects of myeloid cell-specific β2AR deletion on cardiac function and fibrosis following MI in vivo. Altogether, our data reveal a previously unrecognized role for β2AR in the regulation of myeloid cell-dependent efferocytosis in the heart following injury.
Exploring Abstract Pattern Representation in The Brain and Non-symbolic Neural Networks
Authors: Avcu Enes , Gow David 
Published: November 2023

AbstractHuman cognitive and linguistic generativity depends on the ability to identify abstract relationships between perceptually dissimilar items. Marcus et al. (1999) found that human infants can rapidly discover and generalize patterns of syllable repetition (reduplication) that depend on the abstract property of identity, but simple recurrent neural networks (SRNs) could not. They interpreted these results as evidence that purely associative neural network models provide an inadequate framework for characterizing the fundamental generativity of human cognition. Here, we present a series of deep long short-term memory (LSTM) models that identify abstract syllable repetition patterns and words based on training with cochleagrams that represent auditory stimuli. We demonstrate that models trained to identify individual syllable trigram words and models trained to identify reduplication patterns discover representations that support classification of abstract repetition patterns. Simulations examined the effects of training categories (words vs. patterns) and pretraining to identify syllables, on the development of hidden node representations that support repetition pattern discrimination. Representational similarity analyses (RSA) comparing patterns of regional brain activity based on MRI-constrained MEG/EEG data to patterns of hidden node activation elicited by the same stimuli showed a significant correlation between brain activity localized in primarily posterior temporal regions and representations discovered by the models. These results suggest that associative mechanisms operating over discoverable representations that capture abstract stimulus properties account for a critical example of human cognitive generativity.
Ephaptic coupling between olfactory receptor neurons is sensitive to relative stimulus timing: Implications for odour source discrimination
Authors: Raiser Georg , Galizia C. Giovanni , Szyszka Paul 
Published: November 2023

AbstractInsect olfactory receptor neurons (ORNs) are often co-localized within sensilla and exhibit non-synaptic reciprocal inhibition through ephaptic coupling. It has been postulated that this inhibition aids odour source discrimination, as synchronous arrival of different odour molecules (odorants) from a single source should increase ephaptic inhibition, whereas asynchronous arrival of odorants from different sources should decrease ephaptic inhibition. However, it was as yet unknown whether temporal arrival patterns of different odorants indeed modulate ephaptic inhibition, since past studies have focused on ephaptic inhibition of sustained ORN responses to prolonged and constant odour stimuli. However, most natural odour stimuli are not constant but rather transient and fluctuate as a result of dispersion in turbulent plumes in the air. To investigate the role of ephaptic inhibition in olfaction within turbulent environments, we recorded co-localized ORNs in the fruit flyDrosophila melanogasterexposed to dynamic odorant mixtures. We found that ephaptic inhibition does modulate transient ORN responses, and the strength of ephaptic inhibition decreases as the synchrony between arriving odorants decreases. These results support the hypothesis that ephaptic inhibition aids odour source discrimination.
Evidence for a Causal Dissociation of the McGurk Effect and Congruent Audiovisual Speech Perception via TMS
Authors: Ahn EunSeon , Majumdar Areti , Lee Taraz , Brang David 
Published: November 2023

AbstractCongruent visual speech improves speech perception accuracy, particularly in noisy environments. Conversely, mismatched visual speech can alter what is heard, leading to an illusory percept known as the McGurk effect. This illusion has been widely used to study audiovisual speech integration, illustrating that auditory and visual cues are combined in the brain to generate a single coherent percept. While prior transcranial magnetic stimulation (TMS) and neuroimaging studies have identified the left posterior superior temporal sulcus (pSTS) as a causal region involved in the generation of the McGurk effect, it remains unclear whether this region is critical only for this illusion or also for the more general benefits of congruent visual speech (e.g., increased accuracy and faster reaction times). Indeed, recent correlative research suggests that the benefits of congruent visual speech and the McGurk effect reflect largely independent mechanisms. To better understand how these different features of audiovisual integration are causally generated by the left pSTS, we used single-pulse TMS to temporarily impair processing while subjects were presented with either incongruent (McGurk) or congruent audiovisual combinations. Consistent with past research, we observed that TMS to the left pSTS significantly reduced the strength of the McGurk effect. Importantly, however, left pSTS stimulation did not affect the positive benefits of congruent audiovisual speech (increased accuracy and faster reaction times), demonstrating a causal dissociation between the two processes. Our results are consistent with models proposing that the pSTS is but one of multiple critical areas supporting audiovisual speech interactions. Moreover, these data add to a growing body of evidence suggesting that the McGurk effect is an imperfect surrogate measure for more general and ecologically valid audiovisual speech behaviors.
Piezo1 stretch-activated channel activity differs between bone marrow-derived and cardiac tissue-resident macrophages
Authors: Simon-Chica A , Klesen A , Emig R , Chan A , Grün D , Lother A , Hilgendorf I , Ravens U , Kohl P , Schneider-Warme F , Peyronnet R 
Published: November 2023

AbstractMacrophages (MΦ) play pivotal roles in tissue homeostasis and repair. Their mechanical environment recently emerged as a key modulator of various cell functions, and MΦ mechanosensitivity is likely to be critical for cellular activity in particular in a rhythmically contracting organ such as the heart. MΦ,in-vitro-differentiated from bone marrow (MΦBM), form a popular cell model for research. This study explores the activity of stretch-activated ion channels (SAC) in murine MΦBMand compares it to SAC activity in cardiac tissue-resident MΦ (MΦTR). Our main findings are: i) MΦBMand MΦTRhave stretch-induced currents, indicating expression of functional SAC at their plasma membrane; ii) the current profiles in MΦBMand in MΦTRshow characteristics of cation non-selective SAC; iii) unlike in MΦBM, Piezo1 ion channel activity at the plasma membrane of MΦTRis not detectable, neither by assessing electrophysiological activity using the patch clamp technique, nor by measuring cytosolic calcium concentration upon perfusion with Yoda1, a Piezo1 channel agonist. In mature scars after ventricular cryoablation, stretch-induced current characteristics of MΦTRare not significantly different compared to non-injured control tissue, even though scars are expected to contain a mix of pre-existing and circulation-recruited MΦ. This suggests that MΦ invading injured cardiac tissue either phenoconvert their mechanosensitivity from MΦBMto MΦTR, or that thein vitrodifferentiation protocols used to obtain MΦBMgenerate cells that differ from MΦ recruited from the circulation during tissue repairin vivo. Further investigations will explore SAC identity in lineage-traced MΦ in scar tissue, and compare mechanosensitivity of circulating monocytes with that of MΦBM.Key pointsMΦBMand MΦTRhave stretch-induced currents, indicating expression of functional SAC at their plasma membrane;The current profiles in MΦBMand in MΦTRshow characteristics of cation non-selective SAC;Unlike in MΦBM, Piezo1 ion channel activity at the plasma membrane of MΦTRis not detectable
Selective sweep probabilities in spatially expanding populations
Authors: Stein Alexander , Kizhuttil Ramanarayanan , Bak Maciej , Noble Robert 
Published: November 2023

AbstractEvolution during range expansions shapes biological systems from microbial communities and tumours up to invasive species. A fundamental question is whether, when a beneficial mutation arises during a range expansion, it will evade clonal interference and sweep through the population to fixation. However, most theoretical investigations of range expansions have been confined to regimes in which selective sweeps are effectively impossible, while studies of selective sweeps have either assumed constant population size or have ignored spatial structure. Here we use mathematical modelling and analysis to investigate selective sweep probabilities in the alternative yet biologically relevant scenario in which mutants can outcompete and displace a slowly spreading wildtype. Assuming constant radial expansion speed, we derive probability distributions for the arrival time and location of the first surviving mutant and hence find surprisingly simple approximate and exact expressions for selective sweep probabilities in one, two and three dimensions, which are independent of mutation rate. Namely, the selective sweep probability is approximately (1− cwt/cm)d, wherecwtandcmare the wildtype and mutant radial expansion speeds, anddthe spatial dimension. Using agent-based simulations, we show that our analytical results accurately predict selective sweep frequencies in the two-dimensional spatial Moran process. We further compare our results with those obtained for alternative growth laws. Parameterizing our model for human tumours, we find that selective sweeps are predicted to be rare except during very early solid tumour growth, thus providing a general, pan-cancer explanation for findings from recent sequencing studies.
MetaVision3D: Automated Framework for the Generation of Spatial Metabolome Atlas in 3D
Authors: Ma Xin , Shedlock Cameron J. , Medina Terrymar , Ribas Roberto A. , Clarke Harrison A. , Hawkinson Tara R. , Dande Praveen K. , Wu Lei , Burke Sara N. , Merritt Matthew E. , Vander Kooi Craig W. , Gentry Matthew S. , Yadav Nirbhay N. , Chen Li , Sun Ramon C. 
Published: November 2023

AbstractHigh-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics is an emerging field that enables the dissection of the complex metabolic landscape and heterogeneity from a thin tissue section. Currently, spatial metabolism highlights the remarkable complexity in two-dimensional space and is poised to be extended into the three-dimensional world of biology. Here, we introduce MetaVision3D, a novel pipeline driven by computer vision techniques for the transformation of serial 2D MALDI mass spectrometry imaging sections into a high-resolution 3D spatial metabolome. Our framework employs advanced algorithms for image registration, normalization, and interpolation to enable the integration of serial 2D tissue sections, thereby generating a comprehensive 3D model of unique diverse metabolites across host tissues at mesoscale. As a proof of principle, MetaVision3D was utilized to generate the mouse brain 3D metabolome atlas (available athttps://metavision3d.rc.ufl.edu/) as an interactive online database and web server to further advance brain metabolism and related research.
Social determinants of adult COVID-19 vaccine acceptance and uptake in a Brazilian urban informal community: a longitudinal time-to-event study
Authors: Dorión Murilo , Ticona Juan Pablo A. , Fofona Mariam O. , Lind Margaret L. , Nery Nivison , Victoriano Renato , do Aragão Filho Ananias S. , Reis Mitermayer G. , Costa Federico , Ko Albert I. 
Published: November 2023

AbstractResidents of informal urban settlements have a high risk of COVID-19 exposure and have less access to medical care, making vaccine-driven prevention critical in this vulnerable population. Despite robust vaccination campaigns in Brazil, vaccine uptake and timing continue to be influenced by social factors and contribute to health disparities. To address this, we conducted a sequential survey in a cohort of 717 adults in an urbanfavelain Salvador, Brazil where participants were interviewed in 2020, before vaccines were rolled out, and in 2022, after primary and booster dose distribution. We collected data on demographics, social characteristics, and COVID-19 vaccination status and intent. Primary series uptake was high (91.10% for 1stdose and 94.74% for 2nddose among eligible); however, booster uptake was lower (63.51% of eligible population) at the time of the second interview, suggesting a decreasing interest in vaccination. To account for both vaccine refusal and delays, we conducted a Cox time-to-event analysis of dose uptake using sequential independent outcomes. Exposure times were determined by dose eligibility date to account for age and comorbidities. Intent to vaccinate in 2020 (hazard ratio [HR]: 1.54, CI: [1.05, 1.98]) and age (HR: 1.27, CI: [1.01, 2.08]) were associated with higher vaccination rates for the 1stdose. Males were less likely to receive the 1stdose (HR: 0.61, CI: [0.35, 0.83]), and, compared to catholics, 2nddose uptake was lower for those identifying with Pentecostalism (HR: 0.49, CI: [0.37, 0.66]) and without a religion (HR: 0.49, CI: [0.37, 0.66]), with the latter association disappearing after controlling by age. Risk perception was associated with 2nddose uptake (HR: 1.15, CI: [1.08, 1.26]). The role of sex and religion in vaccination behavior highlights the need for targeted outreach and interfacing with local organizations. The data offers lessons to build a long-term COVID-19 vaccination strategy beyond availability.
A Scoping Review of Privacy and Utility Metrics in Medical Synthetic Data
Authors: Kaabachi Bayrem , Despraz Jérémie , Meurers Thierry , Otte Karen , Halilovic Mehmed , Kulynych Bogdan , Prasser Fabian , Raisaro Jean Louis 
Published: November 2023

AbstractThe use of synthetic data is a promising solution to facilitate the sharing and reuse of health-related data beyond its initial collection while addressing privacy concerns. However, there is still no consensus on a standardized approach for systematically evaluating the privacy and utility of synthetic data, impeding its broader adoption. In this work, we present a comprehensive review and systematization of current methods for evaluating synthetic health-related data, focusing on both privacy and utility aspects. Our findings suggest that there are a variety of methods for assessing the utility of synthetic data, but no consensus on which method is optimal in which scenario. Moreover, we found that most studies included in this review do not evaluate the privacy protection provided by synthetic data, and those that do often significantly underestimate the risks.
DrosophilaNeuronal Glucose 6 Phosphatase is a Modulator of Neuropeptide Release that Regulates Muscle Glycogen Stores via FMRFamide Signaling
Authors: Miyamoto Tetsuya , Hedjazi Sheida , Miyamoto Chika , Amrein Hubert 
Published: November 2023

SUMMARYNeuropeptides (NPs) and their cognate receptors are critical effectors of diverse physiological processes and behaviors. We recently reported of a non-canonical function of theDrosophila Glucose-6-Phosphatase(G6P) gene in a subset of neurosecretory cells in the CNS that governs systemic glucose homeostasis in food deprived flies. Here, we show thatG6Pexpressing neurons define 6 groups of neuropeptide secreting cells, 4 in the brain and 2 in the thoracic ganglion. Using the glucose homeostasis phenotype as a screening tool, we find that neurons located in the thoracic ganglion expressing FMRFamide neuropeptides (FMRFaG6Pneurons) are necessary and sufficient to maintain systemic glucose homeostasis in starved flies. We further show thatG6Pis essential inFMRFaG6Pneurons for attaining a prominent Golgi apparatus and secreting neuropeptides efficiently. Finally, we establish thatG6Pdependent FMRFa signaling is essential for the build-up of glycogen stores in the jump muscle which expresses the receptor for FMRFamides. We propose a general model in which the main role ofG6Pis to counteract glycolysis in peptidergic neurons for the purpose of optimizing the intracellular environment best suited for the expansion of the Golgi apparatus, boosting release of neuropeptides and enhancing signaling to respective target tissues expressing cognate receptors.SIGNIFICANCE STATEMENTGlucose-6-phosphtase (G6P) is a critical enzyme in sugar synthesis and catalyzes the final step in glucose production. InDrosophila- and insects in general - where trehalose is the circulating sugar and Trehalose phosphate synthase, and not G6P, is used for sugar production, G6P has adopted a novel and unique role in peptidergic neurons in the CNS. Interestingly, flies lackingG6Pshow diminished Neuropeptide secretions and have a smaller Golgi apparatus in peptidergic neurons. It is hypothesized that the role of G6P is to counteract glycolysis, thereby creating a cellular environment that is more amenable to efficient neuropeptide secretion.