bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Ghost Introgression on Coalescent-based Species Tree Inference and Estimation of Divergence Time
Authors: Pang Xiao-Xu , Zhang Da-Yong 
Published: January 2022

AbstractThe species studied in any evolutionary investigation generally constitute a very small proportion of all the species currently existing or that have gone extinct. It is therefore likely that introgression, which is widespread across the tree of life, involves “ghosts,” i.e., unsampled, unknown, or extinct lineages. However, the impact of ghost introgression on estimations of species trees has been rarely studied and is thus poorly understood. In this study, we use mathematical analysis and simulations to examine the robustness of species tree methods based on a multispecies coalescent model under gene flow sourcing from an extant or ghost lineage. We found that very low levels of extant or ghost introgression can result in anomalous gene trees (AGTs) on three-taxon rooted trees if accompanied by strong incomplete lineage sorting (ILS). In contrast, even massive introgression, with more than half of the recipient genome descending from the donor lineage, may not necessarily lead to AGTs. In cases involving an ingroup lineage (defined as one that diverged no earlier than the most basal species under investigation) acting as the donor of introgression, the time of root divergence among the investigated species was either underestimated or remained unaffected, but for the cases of outgroup ghost lineages acting as donors, the divergence time was generally overestimated. Under many conditions of ingroup introgression, the stronger the ILS was, the higher was the accuracy of estimating the time of root divergence, although the topology of the species tree is more prone to be biased by the effect of introgression.
Weighted transitivity scores that account for triadic edge similarity in undirected graphs
Authors: Peron Guillaume 
Published: January 2022

AbstractThe graph transitivity measures the probability that adjacent vertices in a network are interconnected, thus revealing the existence of tightly connected neighborhoods playing a role in information and pathogen circulation. When the connections vary in strength, focusing on whether connections exist or not can be reductive. I score the weighted transitivity according to the similarity between the weights of the three possible links in each triad. I illustrate the biological relevance of that information with two reanalyses of animal contact networks. In the rhesus macaque Macaca mulatta, a species in which kin relationships strongly predict social relationships, the new metrics revealed striking similarities in the configuration of grooming networks in captive and free-ranging groups, but only as long as the matrilines were preserved. In the barnacle goose Branta leucopsis, in an experiment designed to test the long-term effect of the goslings’ social environment, the new metrics uncovered an excess of weak triplets closed by strong links in males compared to females, and consistent with the triadic process underlying goose dominance relationships.
Magnetic Stimulation Allows Focal Activation of the Mouse Cochlea
Authors: Lee Jae-Ik , Seist Richard , McInturff Stephen , Lee Daniel J. , Brown M. Christian , Stankovic Konstantina M. , Fried Shelley 
Published: January 2022

ABSTRACTCochlear implants (CIs) strive to restore hearing to those with severe to profound hearing loss by artificially stimulating the auditory nerve. While most CI users can understand speech in a quiet environment, hearing that utilizes complex neural coding (e.g., appreciating music) has proved elusive, probably because of the inability of CIs to create narrow regions of spectral activation. Several novel approaches have recently shown promise for improving spatial selectivity, but substantial design differences from conventional CIs will necessitate much additional safety testing before clinical viability is established. Outside the cochlea, magnetic stimulation from small coils (micro-coils) has been shown to confine activation more narrowly than that from conventional micro-electrodes, raising the possibility that coil-based stimulation of the cochlea could improve the spectral resolution of CIs. To explore this, we delivered magnetic stimulation from micro-coils to multiple locations of the cochlea and measured the spread of activation utilizing a multi-electrode array inserted into the inferior colliculus; responses to magnetic stimulation were compared to analogous experiments with conventional micro-electrodes as well as to the responses to auditory monotones. Encouragingly, the extent of activation with micro-coils was ∼60% narrower than that from electric stimulation and largely similar to the spread arising from acoustic stimulation. The dynamic range of coils was more than three times larger than that of electrodes, further supporting a smaller spread of activation. While much additional testing is required, these results support the notion that coil-based CIs can produce a larger number of independent spectral channels and may therefore improve functional performance. Further, because coil-based devices are structurally similar to existing CIs, fewer impediments to clinical translational are likely to arise.
De novo protein structure prediction by incremental inter-residue geometries prediction and model quality assessment using deep learning
Authors: Liu Jun , He Guang-Xing , Zhao Kai-Long , Zhang Gui-Jun 
Published: January 2022

AbstractMotivationThe successful application of deep learning has promoted progress in protein model quality assessment. How to use model quality assessment to further improve the accuracy of protein structure prediction, especially not reliant on the existing templates, is helpful for unraveling the folding mechanism. Here, we investigate whether model quality assessment can be introduced into structure prediction to form a closed-loop feedback, and iteratively improve the accuracy of de novo protein structure prediction.ResultsIn this study, we propose a de novo protein structure prediction method called RocketX. In RocketX, a feedback mechanism is constructed through the geometric constraint prediction network GeomNet, the structural simulation module, and the model quality evaluation network EmaNet. In GeomNet, the co-evolutionary features extracted from MSA that search from the sequence databases are sent to an improved residual neural network to predict the inter-residue geometric constraints. The structure model is folded based on the predicted geometric constraints. In EmaNet, the 1D and 2D features are extracted from the folded model and sent to the deep residual neural network to estimate the inter-residue distance deviation and per-residue lDDT of the model, which will be fed back to GeomNet as dynamic features to correct the geometries prediction and progressively improve model accuracy. RocketX is tested on 483 benchmark proteins and 20 FM targets of CASP14. Experimental results show that the closed-loop feedback mechanism significantly contributes to the performance of RocketX, and the prediction accuracy of RocketX outperforms that of the state-of-the-art methods trRosetta (without templates) and RaptorX. In addition, the blind test results on CAMEO show that although no template is used, the prediction accuracy of RocketX on medium and hard targets is comparable to the advanced methods that integrate templates.AvailabilityThe RocketX web server are freely available athttp://zhanglab-bioinf.com/RocketX.Contactzgj@zjut.edu.cn
ProtFinder: finding subcellular locations of proteins using protein interaction networks
Authors: Grover Aayush , Gatto Laurent 
Published: January 2022

AbstractProtein subcellular localization prediction plays a crucial role in improving our understanding of different diseases and consequently assists in building drug targeting and drug development pipelines. Proteins are known to co-exist at multiple subcellular locations which make the task of prediction extremely challenging. A protein interaction network is a graph that captures interactions between different proteins. It is safe to assume that if two proteins are interacting, they must share some subcellular locations. With this regard, we propose ProtFinder – the first deep learning-based model that exclusively relies on protein interaction networks to predict the multiple subcellular locations of proteins. We also integrate biological priors like the cellular component of Gene Ontology to make ProtFinder a more biology-aware intelligent system. ProtFinder is trained and tested using the STRING and BioPlex databases whereas the annotations of proteins are obtained from the Human Protein Atlas. Our model obtained an AUC-ROC score of 90.00% and an MCC score of 83.42% on a held-out set of proteins. We also apply ProtFinder to annotate proteins that currently do not have confident location annotations. We observe that ProtFinder is able to confirm some of these unreliable location annotations, while in some cases complementing the existing databases with novel location annotations. The source code for ProtFinder is available at https://github.com/UCLouvain-CBIO/ProtFinder.
Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus
Authors: Barbuskaite Dagne , Oernbo Eva K. , Wardman Jonathan H. , Toft-Bertelsen Trine L. , Conti Eller , Andreassen Søren N. , Gerkau Niklas J. , Rose Christine R. , MacAulay Nanna 
Published: January 2022

AbstractElevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we employed in vivo and ex vivo approaches to reveal the efficacy and mode of action of AZE in the rat brain. The drug effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect occurred via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day. Future specific targeting of choroidal carbonic anhydrases may limit the systemic side effects, and therefore enhance the treatment tolerability and effectiveness in select patient groups experiencing elevated ICP.
Considering decoupled phenotypic diversification between ontogenetic phases in macroevolution: An example using Triggerfishes (Balistidae)
Authors: Dornburg Alex , Zapfe Katerina L. , Williams Rachel , Alfaro Michael E. , Morris Richard , Adachi Haruka , Flores Joseph , Santini Francesco , Near Thomas J. , Frédérich Bruno 
Published: January 2022

AbstractAcross the Tree of Life, most studies of phenotypic disparity and diversification have been restricted to adult organisms. However, many lineages have distinct ontogenetic phases that do not reflect the same traits as their adult forms. Non-adult disparity patterns are particularly important to consider for coastal ray-finned fishes, which often have juvenile phases with distinct phenotypes. These juvenile forms are often associated with sheltered nursery environments, with phenotypic shifts between adults and juvenile stages that are readily apparent in locomotor morphology. However, whether this ontogenetic variation in locomotor morphology reflects a decoupling of diversification dynamics between life stages remains unknown. Here we investigate the evolutionary dynamics of locomotor morphology between adult and juvenile triggerfishes. Integrating a time-calibrated phylogenetic framework with geometric morphometric approaches and measurement data of fin aspect ratio and incidence, we reveal a mismatch between morphospace occupancy, the evolution of morphological disparity, and the tempo of trait evolution between life stages. Collectively, our results illuminate how the heterogeneity of morpho-functional adaptations can decouple the mode and tempo of morphological diversification between ontogenetic stages.
Propofol anesthesia alters cortical traveling waves
Authors: Bhattacharya Sayak , Donoghue Jacob A. , Mahnke Meredith , Brincat Scott L. , Brown Emery N. , Miller Earl K. 
Published: January 2022

AbstractOscillatory dynamics in cortex seem to organize into traveling waves that serve a variety of functions. Recent studies show that propofol, a widely used anesthetic, dramatically alters cortical oscillations by increasing slow-delta oscillatory power and coherence. It is not known how this affects traveling waves. We compared traveling waves across the cortex of non-human primates (NHPs) before, during, and after propofol-induced loss-of-consciousness (LOC). After LOC, traveling waves in the slow-delta (∼ 1Hz) range increased, grew more organized, and travelled in different directions relative to the awake state. Higher frequency (8-30 Hz) traveling waves, by contrast, decreased, lost structure, and switched to directions where the slow-delta waves were less frequent. The results suggest that LOC may be due, in part, to changes in slow-delta traveling waves that, in turn, alter and disrupt traveling waves in the higher frequencies associated with cognition.
Spatial MIST Technology for Rapid, Highly Multiplexed Detection of Protein Distribution on Brain Tissue
Authors: Reddy Revanth , Yang Liwei , Liu Jesse , Liu Zhuojie , Wang Jun 
Published: January 2022

AbstractHighly multiplexed analysis of biospecimens significantly advances the understanding of biological basics of diseases, but these techniques are limited by the number of multiplexity and the speed of processing. Here, we present a rapid multiplex method for quantitative detection of protein markers on brain sections with the cellular resolution. This spatial multiplex in situ tagging (MIST) technology is built upon a MIST microarray that contains millions of small microbeads carrying barcoded oligonucleotides. Using antibodies tagged with UV cleavable oligonucleotides, the distribution of protein markers on a tissue slice could be “printed” on the MIST microarray with high fidelity. The performance of this technology in detection sensitivity, resolution and signal-to-noise level has been fully characterized by detecting brain cell markers. We showcase the codetection of 31 proteins simultaneously within 2 h which is about 10 times faster than the other immunofluorescence-based approaches of similar multiplexity. A full set of computational toolkits was developed to segment the small regions and identify the regional differences across the entire mouse brain. This technique enables us to rapidly and conveniently detect dozens of biomarkers on a tissue specimen, and it can find broad applications in clinical pathology and disease mechanistic studies.
Which lower-limb joints compensate for destabilising energy during walking in humans?
Authors: Golyski Pawel R. , Sawicki Gregory S. 
Published: January 2022

AbstractMaintaining stability during perturbed locomotion requires coordinated responses across multiple levels of organization (e.g., legs, joints, muscle-tendon units). However, current approaches to investigating such responses lack a “common currency” that is both shared across scales and can be directly related to perturbation demands. We used mechanical energetics to investigate the demands imposed on a leg by a transient increase in unilateral treadmill belt speed targeted to either early or late stance. We collected full body kinematics and kinetics from 7 healthy participants during 222 total perturbations. From across-subject means, we found early stance perturbations elicited no change in net work exchanged between the perturbed leg and the treadmill but net positive work at the overall leg level, and late stance perturbations elicited positive work at the leg/treadmill interface but no change in net work at the overall leg level. Across all perturbations, changes in ankle and knee work from steady state best reflected changes in overall leg work on the perturbed and contralateral sides, respectively. Broadening this paradigm to include joint level (vs. leg level) perturbations and including muscle-tendon unit mechanical energetics may reveal neuromechanical responses used in destabilizing environments which could inform design of balance-assisting devices and interventions.Subject Areasbiomechanics, biomedical engineering, bioengineering
Exploring the effects of prescribed fire on ticks spread and propagation in a spatial setting
Authors: Fulk Alexander , Huang Weizhang , Agusto Folashade 
Published: January 2022

AbstractLyme disease is one of the most prominent tick-borne diseases in the United States and prevalence of the disease has been steadily increasing over the past several decades due to a number of factors, including climate change. Methods for control of the disease have been considered, one of which is prescribed burning. In this paper the effects of prescribed burns on the abundance of ticks present in a spatial domain are assessed. A spatial stage-structured tick-host model with an impulsive differential equation system is developed to simulate the effect that controlled burning has on tick populations. Subsequently, a global sensitivity analysis is performed to evaluate the effect of various model parameters on the prevalence of infectious nymphs. Results indicate that while ticks can recover relatively quickly following a burn, yearly, high-intensity prescribed burns can reduce the prevalence of ticks in and around the area that is burned. The use of prescribed burns in preventing the establishment of ticks into new areas is also explored and it is observed that frequent burning can slow establishment considerably.
Lower hypothalamus subunit volumes link with long-term growth failure after preterm birth: a longitudinal case-control study
Authors: Ruzok Tobias , Schmitz-Koep Benita , Menegaux Aurore , Eves Robert , Daamen Marcel , Boecker Henning , Rieger-Fackeldey Esther , Priller Josef , Zimmer Claus , Bartmann Peter , Wolke Dieter , Sorg Christian , Hedderich Dennis M. 
Published: January 2022

AbstractBackgroundPreterm birth is associated with an increased risk for impaired growth. While it is known that in prematurity several somatic to environmental factors such as endocrine factors or nutrition modulate short- and long-term growth failure, the contribution of potentially impaired growth control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in growth control is altered after preterm birth, with these alterations being associated with aberrant weight development into adulthood.MethodsWe assessed 101 very preterm (i.e., <32 weeks of gestational age) and/or very low birth weight (i.e., <1500g; VP/VLBW) and 110 full-term born (FT) adults of the population-based Bavarian Longitudinal Study with T1-weighted MRI, deep learning-based hypothalamus subunit segmentation, and multiple body weight assessments from birth into adulthood.ResultsVolumes of the whole hypothalamus and hypothalamus subunits relevant for growth control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and growth trajectories (i.e., trajectory slopes and trajectories of those small for gestational age and with long-term catch-up growth). Concerning VP/VLBW weight trajectories, relatively larger hypothalamic volumes comparable to those of FT adults, especially in subunits including the lateral hypothalamus, were associated with favorable long-term growth trajectories.ConclusionsResults demonstrate lower volumes of growth control-related hypothalamus sub-units after preterm birth that link with long-term growth failure. Data suggest postnatal development of growth-related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body growth trajectories into adulthood.FundingThis study was supported by the Deutsche Forschungsgemeinschaft (BA 6370/2-1 to C.S.), the German Federal Ministry of Education and Science (BMBF 01ER0801 to P.B. and D.W., BMBF 01ER0803 to C.S.) and the Kommission für Klinische Forschung, Technische Universität München (KKF 8700000474 to D.M.H.).
Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity
Authors: Rodda Lauren B. , Morawski Peter A. , Pruner Kurt B. , Fahning Mitchell L , Howard Christian A. , Franko Nicholas , Logue Jennifer , Eggenberger Julie , Stokes Caleb , Golez Inah , Hale Malika , Gale Michael , Chu Helen Y. , Campbell Daniel J. , Pepper Marion 
Published: January 2022

SummaryImmune memory is tailored by cues that lymphocytes perceive during priming. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic created a situation in which nascent memory could be tracked through additional antigen exposures. Both SARS-CoV-2 infection and vaccination induce multifaceted, functional immune memory, but together they engender improved protection from disease, termed “hybrid immunity”. We therefore investigated how vaccine-induced memory is shaped by previous infection. We found that following vaccination, previously infected individuals generated more SARS-CoV-2 RBD-specific memory B cells and variant-neutralizing antibodies and a distinct population of IFN-γ and IL-10-expressing memory SARS-CoV-2 spike-specific CD4+ T cells than previously naive individuals. While additional vaccination could increase humoral memory, it did not recapitulate the distinct CD4+ T cell cytokine profile in previously naive individuals. Thus, imprinted features of SARS-CoV-2-specific memory lymphocytes define hybrid immunity.