bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping Kappa Opioid Receptor Binding in Titi Monkeys with11C-GR103545 PET
Authors: Almeida Alita Jesal D , Hobson Brad A. , Savidge Logan E. , Manca Claudia , Paulus John P. , Bales Karen L. , Chaudhari Abhijit J. 
Published: August 2024

AbstractPurposeThe kappa opioid receptor (KOR) plays a pivotal role in stress- and anxiety-related behaviors, especially in social separation and bonding. However, KOR modulations in these social contexts are not fully characterized. The coppery titi monkey (Plecturocebus cupreus) has been utilized as a translational animal model for studying the neurobiology of attachment, as they form socially monogamous adult pair bonds. While the PET radiotracer11C-GR103545 has shown the ability to track KOR activity in other species, it has not been utilized in titi monkeys. This study assessed11C-GR103545 PET for characterizing KOR activityin vivoand its pharmacological blockade in titi monkeys.MethodsAdult titi monkeys (N=6) underwent11C-GR103545 PET brain scans at baseline, followed by repeat scans upon administration of a KOR antagonist (CERC-501) and a KOR agonist (U50,488). Region-specific, non-displaceable binding potential (BPND) was calculated, with the cerebellum as the reference region, focusing on 14 brain volumes of interest (VOIs) implicated in social bonding.ResultsBaseline11C-GR103545 uptake characteristics across VOIs were consistent with previous reports in humans and other monkey models. CERC-501 pretreatment led to a significant reduction in BPND(average 55.99%) across several, but not all brain VOIs, with the most notable reduction in the superior frontal gyrus (76.25%). In contrast, U50,488 pretreatment resulted in no significant BPNDchanges across the VOIs analyzed.ConclusionsThis study demonstrates the utility of11C-GR103545 to assess KOR binding dynamics in a monkey model of social bonding. Region-specific blockade of KOR was observed after pretreatment by CERC-501, while blockade by the KOR agonist U50,488 did not change11C-GR103545 binding.
Phylogenomics resolve the systematics and biogeography of the ant tribe Myrmicini and tribal relationships within the hyperdiverse ant subfamily Myrmicinae
Authors: Prebus Matthew , Rabeling Christian 
Published: August 2024

ABSTRACTAnts are a globally distributed and highly diverse group of eusocial animals, playing key ecological roles in most of the world’s terrestrial ecosystems. Our understanding of the processes involved in the evolution this diverse family is contingent upon our knowledge of the phylogeny of the ants. While relationships among most subfamilies have come into resolution recently, several of the tribal relationships within the hyperdiverse subfamily Myrmicinae persistently conflict between or within studies, mirroring the controversial relationships of the Leptanillinae and Martialinae to the remaining ant subfamilies. Another persistent issue of debate in ant phylogenetics is the timing of major evolutionary events as inferred via divergence dating. Here, we test the topology of the myrmicine tribes using genome scale data, inspect gene tree-species tree concordance, and use posterior predictive checks and tests of compositional heterogeneity to infer sequence characteristics which potentially introduce systematic bias in myrmicine tribal topology. Furthermore, we test the placement of the fossil †Manica andrannaeby integrating phylogenomic and morphological data from nearly all species within the genusManica,and a broad sampling of its sister genusMyrmica.Subsequently, we demonstrate the effect of fossil placement on overall divergence times in the Myrmicinae. We then re-evaluate the historical biogeography of the Myrmicini and Pogonomyrmecini considering newly generated genetic data and insights from our phylogenomic results. We find that our current understanding of tribal topology in the Myrmicinae is strongly supported, but this topology is highly sensitive to compositional heterogeneity and gene-tree species-tree conflict. Our fossil placement analyses strongly suggest that †Manica andrannaeis a stemManicaspecies, and that placement of this fossil in the crown group affects not only divergence dates within the tribe Myrmicini, but also has broad implications for divergence times throughout the formicoid clade. The results of our biogeographic reconstructions indicate a South American origin for the Pogonomyrmecini + Myrmicini, with the MRCA ofMyrmicainhabiting the western Nearctic in the early Miocene prior to repeated dispersal across Beringia throughout the Miocene and Pliocene. The MRCA ofManica, on the other hand, was inferred to have a Holarctic range prior to vicariance during the Pliocene. Unexpectedly, we found strong support in the Pogonomyrmecini for three coordinated dispersal events from South to Central America during the early Miocene, which has been previously proposed as an early biotic interchange event prior to the more commonly accepted 3.5 Ma closure of the Isthmus of Panama.
Model selection for spectral parameterization
Authors: Wilson Luc E. , Castanheira Jason da Silva , Kinder Benjamin Lévesque , Baillet Sylvain 
Published: August 2024

AbstractNeurophysiological brain activity comprises rhythmic (periodic) and arrhythmic (aperiodic) signal elements, which are increasingly studied in relation to behavioral traits and clinical symptoms. Current methods for spectral parameterization of neural recordings rely on user-dependent parameter selection, which challenges the replicability and robustness of findings. Here, we introduce a principled approach to model selection, relying on Bayesian information criterion, for static and time-resolved spectral parameterization of neurophysiological data. We present extensive tests of the approach with ground-truth and empirical magnetoencephalography recordings. Data-driven model selection enhances both the specificity and sensitivity of spectral and spectrogram decompositions, even in non-stationary contexts. Overall, the proposed spectral decomposition with data-driven model selection minimizes the reliance on user expertise and subjective choices, enabling more robust, reproducible, and interpretable research findings.Lay summaryBrain activity is composed of rhythmic patterns that repeat over time and arrhythmic elements that are less structured. Recent advances in brain signal analysis have improved our ability to distinguish between these two types of components, enhancing our understanding of brain signals. However, current methods require users to adjust several parameters manually to obtain their results. The outcomes of the analyses therefore depend on each user’s decisions and expertise. To improve the replicability of research findings, the authors propose a new, automated method to streamline the analysis of brain signal contents. They developed a new algorithm that defines the parameters of the analytical pipeline informed by the data. The effectiveness of this new method is demonstrated with both synthesized and real-world data. The new approach is made available to all researchers as a free, open-source app, observing best practices for neuroscience research.
Understanding the Sport Viewership Experience using Functional Near-Infrared Spectroscopy
Authors: Potwarka Luke R. , Safati Adrian B. , Pappas Adam T. , Ramchandani Girish , Naraine Michael L. , Gurbez Nur , Hall Peter A. 
Published: August 2024

AbstractSubjective evaluation of a sport event in real time is normally assessed using self-report measures, but neural indices of evaluative processing may provide new insights. The extent of evaluative processing of a sporting event at the neural level may depend on the degree of emotional investment by the viewer, as well as the key moment of the game play being observed. Those with high ego involvement might show more activation within evaluative processing nodes, and this pattern may be most pronounced during critical moments of game play. In the current study, we examined neural activations within the medial and lateral prefrontal cortex during game play as a function of ego-involvement, using video clips featuring key moments in a European league ice hockey game. A total of 343 participants were pre-screened to identify 20 high and low ego-involved individuals. These subgroups then viewed a game segment containing 12 key play moments, while undergoing neuroimaging using fNIRS. Findings indicated more engagement of the dmPFC throughout all key moments for high ego-involved participants, but particularly during critical game moments. Overall, findings suggest that neural indices of evaluative processing might contribute meaningfully to understanding when emotionally invested individuals are most engaged in an action sequence during a sporting event.
Genetics of Cardiac Aging Implicate Organ-Specific Variation
Authors: Brundage James , Barrios Joshua P. , Tison Geoffrey H. , Pirruccello James P. 
Published: August 2024

AbstractHeart structure and function change with age, and the notion that the heart may age faster for some individuals than for others has driven interest in estimating cardiac age acceleration. However, current approaches have limited feature richness (heart measurements; radiomics) or capture extraneous data and therefore lack cardiac specificity (deep learning [DL] on unmasked chest MRI). These technical limitations have been a barrier to efforts to understand genetic contributions to age acceleration. We hypothesized that a video-based DL model provided with heart-masked MRI data would capture a rich yet cardiac-specific representation of cardiac aging.In 61,691 UK Biobank participants, we excluded noncardiac pixels from cardiac MRI and trained a video-based DL model to predict age from one cardiac cycle in the 4-chamber view. We then computed cardiac age acceleration as the bias-corrected prediction of heart age minus the calendar age. Predicted heart age explained 71.1% of variance in calendar age, with a mean absolute error of 3.3 years. Cardiac age acceleration was linked to unfavorable cardiac geometry and systolic and diastolic dysfunction. We also observed links between cardiac age acceleration and diet, decreased physical activity, increased alcohol and tobacco use, and altered levels of 239 serum proteins, as well as adverse brain MRI characteristics.We found cardiac age acceleration to be heritable (h2g 26.6%); a genome-wide association study identified 8 loci related to linked to cardiomyopathy (nearTTN, TNS1, LSM3, PALLD, DSP, PLEC, ANKRD1andMYO18B) and an additional 16 loci (nearMECOM, NPR3, KLHL3, HDGFL1, CDKN1A, ELN, SLC25A37, PI15, AP3M1, HMGA2, ADPRHL1, PGAP3, WNT9B, UHRF1 and DOK5). Of the discovered loci, 21 were not previously associated with cardiac age acceleration. Mendelian randomization revealed that lower genetically mediated levels of 6 circulating proteins (MSRA most strongly), as well as greater levels of 5 proteins (LXN most strongly) were associated with cardiac age acceleration, as were greater blood pressure and Lp(a). A polygenic score for cardiac age acceleration predicted earlier onset of arrhythmia, heart failure, myocardial infarction, and mortality.These findings provide a thematic understanding of cardiac age acceleration and suggest that heart- and vascular-specific factors are key to cardiac age acceleration, predominating over a more global aging program.
Environmental and molecular noise buffering by the cyanobacterial clock in individual cells
Authors: Eremina Aleksandra , Schwall Christian , Saez Teresa , Witting Lennart , Kohlheyer Dietrich , Martins Bruno M.C. , Thomas Philipp , Locke James C.W. 
Published: August 2024

AbstractCircadian clocks enable organisms to anticipate daily cycles, while being robust to molecular and environmental noise. Here, we show how the cyanobacterial clock buffers genetic and environmental perturbations through its core phosphorylation loop. We first characterise single-cell clock dynamics in clock mutants using a microfluidics device that allows precise control of the microenvironment. We find known clock regulators are dispensable for clock robustness, whilst perturbations of the core clock reveal that the wild-type operates at a noise optimum that we can reproduce in a stochastic model of just the core phosphorylation loop. We then examine how the clock responds to noisy environments, including natural light conditions. The model accurately predicts how the clock filters out environmental noise, including fast light fluctuations, to keep time while remaining responsive to environmental shifts. Our findings illustrate how a simple clock network can exhibit complex noise filtering properties, advancing our understanding of how biological circuits can perform accurately in natural environments.
Methodology for the identification and analysis of species associations in biological communities using statistical distributions
Authors: Seleznev Dmitriy G. , Prokin Alexander A. , Kurina Ekaterina M. 
Published: August 2024

AbstractA methodology for identifying pairs of mutually associated and mutually incompatible species pairs based on qualitative ecological data in the ‘species-samples’ format is described. Statistical criteria for assessing the direction and strength of species associations using discrete hypergeometric and binomial distributions are provided. Additionally, there are proposed methods for visualising selected associations using undirected graphs, combining associated species into groups, and analysing them. An open access web application implementing the described methodology is also presented. The methodology is illustrated with data on 37 alien macrozoobenthic species from 255 samples collected in the Volga River reservoirs.
Seeing or believing in hyperplexed spatial proteomics via antibodies. New and old biases for an image-based technology
Authors: Bolognesi Maddalena M , Dall’Olio Lorenzo , Maerten Amy , Borghesi Simone , Castellani Gastone , Cattoretti Giorgio 
Published: August 2024

ABSTRACTHyperplexed in-situ targeted proteomics via antibody immunodetection (i.e. > 15 markers) is changing how we classify cells and tissues. Differently from other high-dimensional single-cell assays (flow cytometry, single cell RNA sequencing), the human eye is a necessary component in multiple procedural steps: image segmentation, signal thresholding, antibody validation and iconographic rendering. Established methods complement the human image evaluation, but may carry undisclosed biases in such a new context, therefore we re-evaluate all the steps in hyperplexed proteomics. We found that the human eye can discriminate less than 64 out of 256 gray levels and has limitations in discriminating luminance levels in conventional histology images. Furthermore, only images containing visible signals are selected and eye-guided digital thresholding separates signal from noise. BRAQUE, a hyperplexed proteomic tool, can extract, in a marker-agnostic fashion, granular information from markers which have a very low signal-to-noise ratio and therefore are not visualized by traditional visual rendering. By analyzing a public human lymph node dataset, we also found unpredicted staining results by validated antibodies, which highlight the need to upgrade the definition of antibody specificity in hyperplexed immunostaining. Spatially hyperplexed methods upgrade and supplant traditional image-based analysis of tissue immunostaining, beyond the human eye contribution.IMPACT STATEMENTStaining with multiple biomarkers a single tissue section, multiplex staining, is changing how we examine in-situ normalcy, pathology and the interrelationship of good and bad biological actors. Bioinformatic pipelines developed to deal with high-dimensional datasets such as single cell RNA sequencing or multiparameter flow-cytometry have been adapted to analogous types of data derived from tissue, and co-exist with conventional image analysis tools and human eye-guided image evaluation. We wanted to evaluate if multiplex staining with more than 15 markers (hyperplexed) has comparable sensitivity to conventional image analysis and if these latter analysis tools carry undisclosed biases and should not be used together with hyperplexed staining. We found that the human eye has a reduced discriminative power for grayscale and luminance levels compared to the 8-bit available spectrum, affecting positive signal recognition above the noise. We also found that the granular analytical power of recent bioinformatic pipelines can extract information from images which defy human eye perception and deliver information unattainable with existing image analysis tools for single-stain images.
Evaluating permutation-based inference for partial least squares analysis of neuroimaging data
Authors: Danyluik Matthew , Zeighami Yashar , Mukora Alice , Lepage Martin , Shah Jai , Joober Ridha , Misic Bratislav , Iturria-Medina Yasser , Chakravarty M. Mallar 
Published: August 2024

AbstractPartial least squares (PLS) is actively leveraged in neuroimaging work, typically to map latent variables (LVs) representing brain-behaviour associations. LVs are considered statistically significant if they tend to capture more covariance than LVs derived from permuted data, with a Procrustes rotation applied to map each set of permuted LVs to the space defined by the originals, creating an “apples to apples” comparison. Yet, it has not been established whether applying the rotation makes the permutation test more sensitive to whether true LVs are present in a dataset, and it is unclear if significance alone is sufficient to fully characterize a PLS decomposition, given that complementary metrics like strength and split-half stability may offer non-redundant information about the LVs. Accordingly, we performed PLS analyses across a range of simulated datasets with known latent effects, observing that the Procrustes rotation systematically weakened the null distributions for the first LV. By extension, the first LV was nearly always significant, regardless of whether the effect was weak, undersampled, noisy, or simulated at all. But, if no rotation was applied, all possible LVs tended to be significant as we increased the sample size of UK Biobank datasets. Meanwhile, LV strength and stability metrics accurately tracked our confidence that effects were present in simulated data, and allowed for a more nuanced assessment of which LVs may be relevant in the UK Biobank. We end by presenting a list of considerations for researchers implementing PLS permutation testing, and by discussing promising alternative tests which may alleviate the concerns raised by our findings.
Sequences within and upstream of the mouse Ets1 gene drive high level expression in B cells, but are not sufficient for consistent expression in T cells
Authors: Kearly Alyssa , Saelee Prontip , Bard Jonathan , Sinha Satrajit , Satterthwaite Anne , Garrett-Sinha Lee Ann 
Published: August 2024

AbstractThe levels of transcription factor Ets1 are high in resting B and T cells, but are downregulated by signaling through antigen receptors and Toll-like receptors (TLRs). Loss of Ets1 in mice leads to excessive immune cell activation and development of an autoimmune syndrome and reduced Ets1 expression has been observed in human PBMCs in the context of autoimmune diseases. In B cells, Ets1 serves to prevent premature activation and differentiation to antibody-secreting cells. Given these important roles for Ets1 in the immune response, stringent control ofEts1gene expression levels is required for homeostasis. However, the genetic regulatory elements that control expression of theEts1gene remain relatively unknown. Here we identify a topologically-associating domain (TAD) in the chromatin of B cells that includes the mouseEts1gene locus and describe an interaction hub that extends over 100 kb upstream and into the gene body. Additionally, we compile epigenetic datasets to find several putative regulatory elements within the interaction hub by identifying regions of high DNA accessibility and enrichment of active enhancer histone marks. Using reporter constructs, we determine that DNA sequences within this interaction hub are sufficient to direct reporter gene expression in lymphoid tissues of transgenic mice. Further analysis indicates that the reporter construct drives faithful expression of the reporter gene in mouse B cells, but variegated expression in T cells, suggesting the existence of T cell regulatory elements outside this region. To investigate how the downregulation of Ets1 transcription is associated with alterations in the epigenetic landscape of stimulated B cells, we performed ATAC-seq in resting and BCR-stimulated primary B cells and identified four regions within and upstream of theEts1locus that undergo changes in chromatin accessibility that correlate toEts1gene expression. Interestingly, functional analysis of several putative Ets1 regulatory elements using luciferase constructs suggested a high level of functional redundancy. Taken together our studies reveal a complex network of regulatory elements and transcription factors that coordinate the B cell-specific expression ofEts1.
Octopus can use odor plumes to find food
Authors: Weertman Willem Lee , Gopal Venkatesh , Sivitilli Dominic M. , Scheel David , Gire David H. 
Published: August 2024

AbstractOdor-plume-guided navigation, tracking an odor plume to its source, is a primordial behavior used by most animals to search beyond the visual range. Here we report the first laboratory observations of octopuses performing this behavior, demonstrating that they can use odor plumes to find food. In a three-station discrimination task carried out in the dark, octopus showed a strong preference to move upstream towards the food-baited target, supporting the hypothesis that they are performing odor-guided search. When seeking a single baited target, also in the dark, octopuses not only preferred to move upstream towards the food source, but they also displayed characteristic motions associated with odor-gated rheotaxis, a commonly used odor tracking strategy used by many animals, which includes pausing, switchbacks, and across-stream redirections to the bait. Additionally, when approaching single baited stations the octopus often made reactive fast lunging motions. The observation of these fastarm-alignedmotions (FAAM), taken together with the observation that the octopus did not have a characteristic body axis orientation to the bait, as would be expected if bilaterally symmetric organs such as the olfactory pits guided this behavior, supports the hypothesis that the suckers are the primary chemosensory organs driving octopus odor-guided behaviors.