bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the replicability of diffusion weighted MRI-based brain-behavior models
Authors: Kotikalapudi Raviteja , Kincses Balint , Gallitto Giuseppe , Englert Robert , Hoffschlag Kevin , Li Jialin , Bingel Ulrike , Spisak Tamas 
Published: July 2024

ABSTRACTEstablishing replicable inter-individual brain-wide associations is key to advancing our understanding of the crucial links between brain structure, function, and behavior, as well as applying this knowledge in clinical contexts. While the replicability and sample size requirements for anatomical and functional MRI-based brain-behavior associations have been extensively discussed recently, systematic replicability assessments are still lacking for diffusion-weighted imaging (DWI), despite it being the dominant non-invasive method to investigate white matter microstructure and structural connectivity. We report results of a comprehensive evaluation of the replicability of various DWI-based multivariate brain-behavior models. This evaluation is based on large-scale data from the Human Connectome Project, including five different DWI-based brain features (from fractional anisotropy to structural connectivity) and 58 different behavioral phenotypes. Our findings show an overall moderate replicability, with 24-31% of phenotypes replicable with sample sizes of fewer than 500. As DWI yields trait-like brain features, we restricted the analysis to trait-like phenotypes, such as cognitive and motor skills, and found much more promising replicability estimates, with 67-75% of these phenotypes replicable with n<500. Contrasting our empirical results to analytical replicability estimates substantiated that the replicability of DWI-based models is primarily a function of the true, unbiased effect size. Our work highlights the potential of DWI to produce replicable brain-behavior associations. However, it shows that achieving replicability with small-to-moderate samples requires stable, reliable and neurobiologically relevant target phenotypes. Our work highlights the potential of DWI to produce replicable brain-behavior associations, but only for stable, reliable and neurobiologically relevant target phenotypes.HIGHLIGHTSModerate replicability in DWI-based models:Overall replicability of DWI-based brain-behavior associations ranges from 24-31% with sample sizes under 500.Improved replicability for trait-like phenotypes:Trait-like phenotypes e.g., cognitive and motor skills exhibit higher replicability estimates of 67-75%, compared to state-like phenotypes such as emotion.Effect size as a key factor:Replicability is primarily influenced by the true, unbiased effect size, highlighting the importance of targeting stable and reliable phenotypes.Promise of -based multivariate associations:DWI-based brain-behaviour models should focus on phenotypes that display a sufficient temporal stability and test-retest reliability.
Global thermal tolerance of freshwater invertebrates and fish
Authors: Bayat Helena S. , He Fengzhi , Madariaga Graciela M. , Escobar-Sierra Camilo , Prati Sebastian , Jupke Jonathan F. , Peters Kristin , Chen Xing , Spaak Jurg W. , Manfrin Alessandro , Juvigny-Khenafou Noel P.D. , Schäfer Ralf B. 
Published: July 2024

AbstractScientists have investigated the thermal tolerance of organisms for centuries, yet the field has not lost relevance as the environmental threats of thermal pollution and global change sharpen the need to understand the thermal vulnerability of organisms in landscapes increasingly subjected to multiple stressors. Freshwater fish and especially invertebrates are greatly underrepresented in recent large-scale compilations of thermal tolerance, despite the importance of freshwater habitats as a crucial resource and biodiversity havens. This inspired us to create a thermal tolerance database for these organisms that includes literature from 1900 until the present day sourced from five languages to counteract geographic bias, and 395 thermal tolerance tests conducted with additional stressors present. The database contains over 5000 records for over 800 species, including 452 invertebrates, providing a valuable resource to test hypotheses on thermal risks to freshwater organisms in present and future environments, and how these might change in multiple stressor scenarios.
Phylogenetic analysis reveals how selection and mutation shape the coevolution of mRNA and protein abundances
Authors: Cope Alexander L. , Schraiber Joshua G. , Pennell Matt 
Published: July 2024

AbstractThe regulatory mechanisms that shape mRNA and protein abundances are intensely studied. Much less is known about the evolutionary processes that shape the relationship between these two levels of gene expression. To disentangle the contributions of mutational and selective processes, we derive a novel phylogenetic model and fit it to multi-species data from mammalian skin tissue. We find that over macroevolutionary time: 1) there has been strong stabilizing selection on protein abundances; 2) mutations impacting mRNA abundances have minimal influence on protein abundances; 3) mRNA abundances are under selection to track protein abundances, and 4) mRNA abundances adapt more quickly than protein abundances due to increased mutational opportunity. We find additional support for these findings by comparing gene-specific parameter estimates from our model to human functional genomic data. More broadly, our new phylogenetic approach provides a foundation for testing hypotheses about the processes that led to divergence in gene expression.
Population density drives increased parasitism via greater exposure and reduced resource availability in wild hosts
Authors: Hasik Adam Z. , Butt Shane , Maris Katie , Morris Sean , Morris Ali , Turner Richard S. , Pemberton Josephine M. , Albery Gregory F. 
Published: July 2024

AbstractExposure to environmental parasites should increase with host population density due to the accumulation of infective parasites in space. However, competition for resources also increases with density, lowering condition and increasing susceptibility, which offers an alternative pathway for density-dependent infection to act. To test how these two processes act independently or together to drive greater parasite counts, we used a long-term study of red deer to examine associations between host density, resource availability, and counts of three common helminth parasites. We found that greater density correlated with reduced resource availability, and while density was positively associated with both strongyle and tissue worm burdens, resource availability was independently and negatively associated with the same burdens, supporting separate roles of density-dependent exposure and susceptibility in driving infection. This study provides evidence that competition for resources is an important driver of infection in higher-density areas, exacerbating the effects of density-dependent increases in exposure.
ANASFV: a workflow for ASFV whole genome sequencing, assembly, and evaluation
Authors: Li Ke , Han Xu , Shao Yanwen , Zhang Yiwen , Zhao Xiaomin , Johnson Eager Wayne , Li Runsheng 
Published: July 2024

AbstractAfrican Swine Fever Virus (ASFV) poses an ongoing threat with widespread outbreaks affecting both domestic and wild pig populations globally. Effective management of ASFV outbreaks necessitates a deep understanding of its genetic diversity and evolutionary dynamics. Despite the advantages of nanopore sequencing for genome analysis, its application to ASFV genomes encounters specific challenges, such as high host DNA contamination that reduces viral genome coverage and an inherently higher error rate producing small insertions and deletions (indels). Another notable issue is the lack of standardized methods for assessing the quality of ASFV genomes. Furthermore, an increasing number of recombinant isolates of genotype I and II, have been observed, further complicating the task of phylogenetic analysis. To overcome these obstacles, we developed the ANASFV (analysis of an ASFV) pipeline. The pipeline is used to solve four tasks: In the first task, the pipeline introduces an amplicon sequencing approach that significantly improves genomic coverage, enabling reliable genome assembly. The pipeline also introduce reference-aided polishing techniques to correct small indels caused by nanopore sequencing errors. Moving on to the second task, a genome quality assessment system was established to evaluate the completeness and accuracy of the assembled genomes. For the third task, a method to rapidly analyze whether an isolate is a recombinant between genotype I and II, as well as to determine the pattern of recombination, based on gene similarity. Lastly, a comprehensive phylogenetic analysis based on coding sequences (CDS) was conducted, allowing us to generate a refined phylogenetic tree that includes all known ASFV genomes. The ANASFV pipeline will facilitate ASFV full genome sequencing using the nanopore platform. The pipeline will also support robust downstream bioinformatic analyses to assess genome integrity and conduct detailed phylogenetic studies based on whole-genome data.
Aberrant remodelling of astrocytic architecture in acute hepatic encephalopathy: complexity of oedematic atrophic astrocytes
Authors: Popek Mariusz , Obara-Michlewska Marta , Szewczyk Łukasz , Kołodziej Marcin , Verkhratsky Alexei , Albrecht Jan , Zielińska Magdalena 
Published: July 2024

AbstractHepatic encephalopathy (HE) following acute liver failure (ALF) is a primary toxic astrocytopathy, although in-depth characterisation of underlying pathogenesis is far from complete. Among the multitude of astrocyte-specific proteins guiding brain functionality, plasmalemma-cytoskeletal linker ezrin, actin-binding protein profilin-1, and water channel aquaporin 4 (AQP4) contribute to astrocytic morphological plasticity through regulation of cell shape, volume, complexity of primary and terminal processes, and positioning astrocytes against other CNS constituents. Changes in these proteins might contribute to the brain oedema and astrocytic morphological remodelling in the HE. Using transmission electron microscopy, confocal fluorescent microscopy, and 3D reconstruction, we found complex morphological alterations of cortical astrocytes in mice with azoxymethane-induced ALF. Astrocytic primary branches demonstrated hypertrophy, whereas terminal leaflets showed atrophy quantified by the reduced area occupied by astrocytes, decreased number and the length of leaflets, decreased leaflets volume fraction, and altered astrocyte-to-neurone landscape. These morphological changes correlat with decreased expression of AQP4, phosphorylated leaflet-associated ezrin, and the actin dynamics regulator, profilin 1, suggesting the contribution of these proteins to astrocytic pathological remodelling. Pathological changes in astrocytes develop in parallel, and are likely causally linked to, the HE-linked neurological decline, manifested by a reduction in electroencephalography power and by excessive glutamate in the brain microdialysates.Abstract FigureGraphical abstract:Hepatic encephalopathy is associated with astrocyte remodelling manifested by swelling of the soma and primary branches together with atrophy of distal branches and leaflets; the latter retract from synapses thus affecting neurotransmission and contribute to the reduced neuronal activity. Astrocyte remodelling was linked to (and probably instigated by) a decrease of plasmalemma-cytoskeleton linker phosphorylated ezrin (Phos-ezrin), actin modulator profilin-1 (PFN1) and water channel aquaporin 4 (AQP4).
A robust relationship between robustness and evolvability
Authors: Hardy Nate B 
Published: July 2024

AbstractHere, I consolidate and extend simple models of how genetic robustness affects the evolvability of phenotypes with discrete states. I share three main insights. (1) What we already know about the effects of mutational robustness on evolvability can be readily transferred to environmental robustness. (2) Even without a hard genotype-level trade-off between robustness and evolvability, the optimal level of phenotypic robustness depends on the rate of environmental change. But counter-intuitively, when adaptive landscapes are complex, an increase in environmental stability can increase the frequency of environmentally-robust but mutationally-sensitive genotypes. (3) Even with a fixed probability that a mutation is neutral, populations can evolve along the spectrum of robustness and evolvability by evolving the genotype-determined neighborhood of mutationally-accessible phenotypes. Indeed, because it allows for the evolution of increased evolvability without a concomitant increase in genetic load, selection should favor changes in the phenotypic neighborhood over changes in mutational sensitivity.Teaser TextModels of the evolution of discrete phenotypes show that their evolvability is highest when environments fluctuate at intermediate rates, and with intermediate levels of mutational robustness. By merging previous models and relaxing previous assumptions, I show that previous insights are robust. I also show that the same models tell us very different things about the evolvability of discrete traits, namely, that what applies to robustness against mutation is readily transferable to robustness against environmental perturbation, and that selection for evolvability will preferentially work on the neighborhood of mutationally-accessible phenotypes rather than the probability of non-neutral mutation.
Entangled and non-modular enhancer sequences producing independent spatial activities
Authors: Museridze Mariam , Ceolin Stefano , Mühling Bettina , Ramanathan Srishti , Barmina Olga , Sekhar Pallavi Santhi , Gompel Nicolas 
Published: July 2024

AbstractThe modularity of transcriptional enhancers (1, 2) is central to our understanding of morphological evolution, as it allows specific changes to a gene expression pattern component, without affecting others (3). Enhancer modularity refers to physically separated stretches of regulatory sequence producing discrete spatiotemporal transcriptional activity. This concept stems mainly from assays that test the sufficiency of a DNA segment (4) to drive spatial reporter expression resembling that of the corresponding gene. Focusing on sufficiency to produce spatial patterns, it overlooks quantitative aspects of gene expression, underestimating the regulatory sequence actually required to reach full endogenous expression levels. Here we show that five regulatory activities of the pigmentation geneyellowinDrosophila, classically described as modular (5–7), result from extensively overlapping sequences, with broadly distributed regulatory information. Nevertheless, the independent regulatory activities of these entangled enhancers appear to be nucleated by specific segments that we called enhancer cores. Our work calls for a reappraisal of enhancer definition and properties, as well as of the consequences on regulatory evolution.
A multi-region recurrent circuit for evidence accumulation in rats
Authors: Gupta Diksha , Kopec Charles D. , Bondy Adrian G. , Luo Thomas Z. , Elliott Verity A. , Brody Carlos D. 
Published: July 2024

AbstractDecision-making based on noisy evidence requires accumulating evidence and categorizing it to form a choice. Here we evaluate a proposed feedforward and modular mapping of this process in rats: evidence accumulated in anterodorsal striatum (ADS) is categorized in prefrontal cortex (frontal orienting fields, FOF). Contrary to this, we show that both regions appear to be indistinguishable in their encoding/decoding of accumulator value and communicate this information bidirectionally. Consistent with a role for FOF in accumulation, silencing FOF to ADS projections impacted behavior throughout the accumulation period, even while nonselective FOF silencing did not. We synthesize these findings into a multi-region recurrent neural network trained with a novel approach. In-silico experiments reveal that multiple scales of recurrence in the cortico-striatal circuit rescue computation upon nonselective FOF perturbations. These results suggest that ADS and FOF accumulate evidence in a recurrent and distributed manner, yielding redundant representations and robustness to certain perturbations.
Host-use Drives Convergent Evolution in Clownfish and Disentangles the Mystery of an Iconic Adaptive Radiation
Authors: Gaboriau T. , Marcionetti A. , Garcia Jimenez A. , Schmid S. , Fitzgerald L. M. , Micheli B. , Titus B. , Salamin N. 
Published: July 2024

AbstractClownfishes (Amphiprioninae) are a fascinating example of marine radiation. From a central Pacific ancestor, they quickly colonized the coral reefs of the Indo-Pacific and diversified independently on each side of the Indo-Australian Archipelago. Their association with venomous sea anemones is often thought to be the key innovation that enabled the clownfish radiation. However, this intuition has little empirical or theoretical support given our current knowledge of the clade. To date, no ecological variable has been identified that can explain clownfish niche partitioning, phenotypic evolution, species co-occurrence, and thus, the adaptive radiation of the group. Our synthetic work solves this long-standing mystery by testing the influence of sea anemone host use on phenotypic divergence. We provide the first major revision to the known clownfish-sea anemone host associations in over 30 years, accounting for host associations in a biologically relevant way. We gathered whole-genome data for all 28 clownfish species and reconstructed a fully supported species tree for the Amphiprioninae. Integrating this new data into comparative phylogenomic approaches, we demonstrate for the first time, that the host sea anemones are the drivers of convergent evolution in clownfish color pattern and morphology. During the adaptive radiation of this group, clownfishes in different regions that associate with the same hosts have evolved the same phenotypes. Comparative genomics also reveals several genes under convergent positive selection linked to host specialisation events. Our results identify the sea anemone host as the key ecological variable that disentangles the entire adaptive radiation. As one of the most recognizable animals on the planet and an emerging model organism in the biological sciences, our findings bear on the interpretation of dozens of prior studies on clownfishes and will radically reshape research agendas for these iconic organisms.
Multi-dataset Integration and Residual Connections Improve Proteome Prediction from Transcriptomes using Deep Learning
Authors: Cranney Caleb W. , Meyer Jesse G. 
Published: July 2024

AbstractProteomes are well known to poorly correlate with transcriptomes measured from the same sample. While connected, the complex processes that impact the relationships between transcript and protein quantities remains an open research topic. Many studies have attempted to predict proteomes from transcriptomes with limited success. Here we use publicly available data from the Clinical Proteomics Tumor Analysis Consortium to show that deep learning models designed by neural architecture search (NAS) achieve improved prediction accuracy of proteome quantities from transcriptomics. We find that this benefit is largely due to including a residual connection in the architecture that allows input information to be remembered near the end of the network. Finally, we explore which groups of transcripts are functionally important for protein prediction using model interpretation with SHAP.
Calibration of instrumented treadmills using an instrumented pole; a modified version to use relatively smaller forces
Authors: Hosseini-Yazdi Seyed-Saleh 
Published: July 2024

AbstractThe instrumented treadmills’ quality of the generated Ground Reaction Forces (GRF) may degrade over time, as the original calibration matrix may not accurately represent the exerted forces. A cost-effective alternative to manufacturer recalibration is to use an instrumented pole for calibration. Collins et al. presented a simple method to collect multiple data points by exerting forces in various directions. The sensor on the instrumented pole provides instantaneous force magnitudes, while motion capture records the pole’s instantaneous directions. They recommended a relatively large force magnitude (1000N), requiring at least two individuals. Using an optimization method, the new calibration may be estimate by relating the exerted forces (pole) to the treadmill signals. Here, we attempted to simplify the process further, allowing a single individual to perform force exertion with additional force exertion direction. Thus, the calibrating forces were reduced to one-third of the prior recommendation. This maintained the structural integrity of the pole and helped avoid inducing bending moments that could affect calibration results. The cross-validation score for test data (prediction score) was at least 0.92. Additionally, comparing GRFs in posterior/anterior and vertical directions with a benchmark treadmill for even walking revealed an average cross-correlation of 0.97.
Interoceptive Signals Bias Decision Making in Rhesus Macaques
Authors: Cardenas Michael A. , Le Ryan P. , Champ Tess M. , O’Neill Derek , Fuglevand Andrew J. , Gothard Katalin M. 
Published: July 2024

AbstractSeveral influential theories have proposed that interoceptive signals, sent from the body to the brain, contribute to neural processes that coordinate complex behaviors. We altered the physiological state of the body using compounds that have minimal effect on the brain and evaluated their effect on decision-making in rhesus monkeys. We used glycopyrrolate, a non-specific muscarinic (parasympathetic) antagonist, and isoproterenol, a beta-1/2 (sympathetic) agonist, to create a sympathetic-dominated state in the periphery, that was indexed by increased heart rate. Rhesus monkeys were trained on two variants of an approach-avoidance conflict task. The tasks offered a choice between enduring mildly aversive stimuli in exchange for a steady flow of rewards, or cancelling the aversive stimuli, forgoing the rewards. The delay to interrupt the aversive stimuli was used as a measure of monkeys’ tolerance for contact with a hot but not painful stimulus or airflow directed at their muzzle. Both drugs reduced tolerance for the aversive stimuli. To determine whether the drug-induced autonomic state reduced the subjective value of the reward, we tested the effects of glycopyrrolate on a food preference task. Food preference was unaltered, suggesting that the sympathetic dominated state in the periphery selectively reduces tolerance for aversive stimuli without altering reward-seeking behaviors. As the drugs used are expected to have little or no direct effect on the brain, the observed biases in decision making are likely induced by interoceptive afferents that signal to the brain the physiological state of the body.Significance statementThe brain adjusts body physiology to the behavioral agenda of the organism through autonomic efferents; concomitantly interoceptive afferents carry signals that inform the brain about the physiological state of the body, closing a homeostatic regulatory loop. Persuasive theories proposed that interoceptive afferents contribute to higher cognitive functions, including emotion. Empirical evidence that these signals are sufficient to bias complex behavior has been limited by the difficulty of isolating interoceptive afferents from the rest of the homeostatic loop. Here we selectively manipulated the autonomic state of the body using drugs with limited penetrance of the brain in macaques performing decision-making tasks. Sympathetic-dominated peripheral states significantly altered decision making, suggesting that changes in interoceptive afferent signals are sufficient to bias behavior.