bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humans, rats and mice show species-specific adaptations to sensory statistics in categorisation behaviour
Authors: Pedrosa Victor , Menichini Elena , Pajot-Moric Quentin , Vincent Peter , Zhou Liang , Teachen Lillianne , Latham Peter , Akrami Athena 
Published: February 2023

AbstractOne key aspect of animal intelligence is the ability to find, represent and update knowledge of statistical regularities in the sensory environment, in service of adaptive behaviour. This allows animals to build appropriate priors, in order to disambiguate noisy inputs, make predictions and act more efficiently. Here, we compare human, rat, and mouse performance on a 2-alternative-forced-choice sound categorisation task. Importantly, we manipulate the stimulus statistics without affecting the overall weight of each category, and we investigate decision-making in such distinct ‘statistical contexts’ associated with different stimulus prior probabilities. Humans, rats, and mice develop a sensory-dependent bias that increases reward to a near-optimal level. We also explore how flexible animals are in learning different types of statistics, without any explicit cue, when switching from one prior probability to another. All species can adapt to a new underlying distribution by gradually shifting their psychometric behaviour after the switch to a new statistical context, with mice showing the slowest rate of adaptation. Despite the overall sensory-dependent bias that is similar across species, humans versus rodents show distinct trial-to-trial learning updates. Rodents show an overall win-stay choice bias, with rats incorporating decision confidence more strongly than mice. Humans, on the other hand, show a more complex learning update, and more indicative of utilising detailed sensory statistics. We propose two classes of computational models, a boundary learning (discriminative) and a stimulus-category learning (generative) model. We show how they can account for the optimal exploitation of the sensory statistics, and predict the observed species-specific trial-to-trial updates.
Mangrove propagules are limited in their capacity to disperse across long distances
Authors: Granville Natasha R. , Banks-Leite Cristina 
Published: February 2023

AbstractMangroves are subject to rapid and large-scale habitat changes which threaten their unique genetic diversity and provision of critically important ecosystem services. Habitat fragmentation reduces connectivity which can impair dispersal and lead to genetic isolation. However, it is unclear whether fragmentation could impact mangrove genetic isolation, as mangrove propagules can disperse long distances. Here, we conducted a meta-analysis of studies reporting a correlation between geographic distance and genetic distance in mangrove plants. From the 22 studies that met the inclusion criteria, we found a significant isolation-by-distance effect; geographic distance was significantly associated with Nei’s genetic distance and FST. Our results show that mangrove propagules may be limited in their capacity to disperse across long distances, which highlights the importance of maintaining close proximity between habitat patches and reducing habitat fragmentation.
Analysis of the Distal Urinary Tract in Larval and Adult Zebrafish Reveals Unrecognized Homology to the Human System
Authors: Jubber Ibrahim , Morhardt Duncan R , Griffin Jonathan , Cumberbatch Marcus , Glover Maggie , Zheng Yang , Rehman Ishtiaq , Loynes Catherine , Hussain Syed A , Renshaw Stephen A , Leach Steven D , Cunliffe Vincent T , Catto James WF 
Published: February 2023

AbstractLittle is known about the distal excretory component of the urinary tract inDanio rerio(zebrafish). This component is affected by many human diseases and disorders of development. Here, we undertook multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish.In silicosearches identifieduroplakin 1a, 2-likeand3-likegenes in the zebrafish genome (orthologues to genes that encode proteins that characterise the urothelium in humans).In situhybridization demonstrateduroplakin-1aexpression in the zebrafish pronephros and cloaca from 96 hours post-fertilisation. H&E sectioning of adult zebrafish demonstrated two mesonephric ducts uniting into a urinary bladder which leads to a distinct urethral opening. Immunohistochemistry identified Uroplakin 1a and 2 expression within the urothelial luminal surface and Gata3 expression in cell layers that match human urothelial expression. Fluorescent dye injections demonstrated urinary bladder function, including urine storage, intermittent micturition, and a urethral orifice separate from the larger anal canal and rectum. Our findings reveal homology between the urinary tracts of zebrafish and humans and offer the former as a model system to study disease.Summary StatementThe excretory components of the distal urinary tract in larval and adult zebrafish have been incompletely evaluated. Here, we demonstrate close homology in urinary tract anatomy between zebrafish and human, including the presence of a distinct adult urinary bladder capable of periodic micturition
Hypermetabolism in mice carrying a near complete human chromosome 21
Authors: Sarver Dylan C. , Xu Cheng , Rodriguez Susana , Aja Susan , Jaffe Andrew E. , Gao Feng J. , Delannoy Michael , Periasamy Muthu , Kazuki Yasuhiro , Oshimura Mitsuo , Reeves Roger H. , Wong G. William 
Published: February 2023

ABSTRACTThe consequences of aneuploidy have traditionally been studied in cell and animal models in which the extrachromosomal DNA is from the same species. Here, we explore a fundamental question concerning the impact of aneuploidy on systemic metabolism using a non-mosaic transchromosomic mouse model (TcMAC21) carrying a near complete human chromosome 21. Independent of diets and housing temperatures, TcMAC21 mice consume more calories, are hyperactive and hypermetabolic, remain consistently lean and profoundly insulin sensitive, and have a higher body temperature. The hypermetabolism and elevated thermogenesis are due to sarcolipin overexpression in the skeletal muscle, resulting in futile sarco(endo)plasmic reticulum Ca2+ATPase (SERCA) activity and energy dissipation. Mitochondrial respiration is also markedly increased in skeletal muscle to meet the high ATP demand created by the futile cycle. This serendipitous discovery provides proof-of-concept that sarcolipin-mediated thermogenesis via uncoupling of the SERCA pump can be harnessed to promote energy expenditure and metabolic health.
Why do young readers vary in reading fluency? The impact of word length and frequency in French 6th graders
Authors: Lubineau Marie , Watkins Cassandra Potier , Glasel Hervé , Dehaene Stanislas 
Published: February 2023

AbstractPurposeWhich processes induce variations in reading speed in young readers with the same amount of education, but different levels of reading fluency? Here, we tested a prediction of the dual-route model: as fluency increases, these variations may reflect a decreasing reliance on decoding and an increasing reliance on the lexical route.Method1,500 French 6thgraders passed a one-minute speeded reading-aloud task evaluating fluency, and a 10-minute computerized lexical decision task evaluating the impact of word length, word frequency and pseudoword type.ResultsAs predicted, the word length effect varied dramatically with reading fluency, with the least fluent group showing a length effect even for frequent words. The frequency effect also varied, but solely in proportion to overall slowness, suggesting that frequency affects the decision stage in all readers, while length impacts poor readers disproportionately. Response times and errors were also affected by pseudoword type (e.g. letter substitutions or transpositions), but these effects did not vary much with fluency. Overall, lexical decision variables were excellent predictors of reading fluency (r=0.62).ConclusionOur results call attention to middle-school reading difficulties and encourage the use of lexical decision as a test of students’ mental lexicon and the automatization of reading.
A Novel Approach to T-Cell Receptor Beta Chain (TCRB) Repertoire Encoding Using Lossless String Compression
Authors: Konstantinovsky Thomas , Yaari Gur 
Published: February 2023

AbstractT-cell diversity is crucial for producing effective receptors that can recognize the pathogens encountered throughout life. A stochastic biological process known as VDJ recombination accounts for the high diversity of these receptors, making their analysis challenging. We present a new approach to sequence encoding and analysis, based on the Lempel-Ziv 76 algorithm (LZ-76). By creating a graph-like model, we identify specific sequence features and produce a new encoding approach to an individual’s repertoire. We demonstrate that this repertoire representation allows for various applications, such as generation probability inference, informative feature vector derivation, sequence generation, and a new measure for diversity estimation.
TGF-β downregulates antigen processing and presentation genes and MHC I surface expression through a Smad3-dependent mechanism
Authors: Berglund Alix K. , Hinson Anna L. , Schnabel Lauren V. 
Published: February 2023

AbstractRegulation of MHC I surface expression by TGF-β is important for controlling cell-mediated immune responses, but how TGF-β downregulates MHC I is unknown. We investigated this mechanism using flow cytometry and RNA-sequencing to identify the major TGF-β signaling pathway and target genes involved. All three isoforms of TGF-β were found to have similar abilities to downregulate constitutive MHC I surface expression. Inhibiting the type I TGF-β receptor, ALK5, as well the canonical TGF-β signaling molecule Smad3, prevented TGF-β from downregulating MHC I surface expression. RNA-sequencing from horse and human mesenchymal stem cells revealed that multiple genes associated with antigen processing and presentation were downregulated in TGF-β-treated cells with B2M and ERAP1 being downregulated in both species. While downregulation of MHC I surface expression a slow process that continued past 24 hours after TGF-β treatment, downregulation of gene expression of ERAP1 occurred within 12 hours after treatment. B2M expression was not consistently downregulated until after 24 hours and TAP2 expression was inconsistent over a 72-hour period, although it was significantly downregulated at 12 hours after TGF-β treatment. This data supports that TGF-β downregulates antigen processing and presentation genes resulting in decreased surface expression of MHC I through a Smad3-dependent mechanism.
A compact multifunctional model of the rabbit atrioventricular node with dual pathways
Authors: Ryzhii Maxim , Ryzhii Elena 
Published: February 2023

ABSTRACTThe atrioventricular node (AVN) is considered a “black box”, and the functioning of its dual pathways remains controversial and not fully understood. In contrast to numerous clinical studies, there are only a few mathematical models of the node. In this paper, we present a compact, computationally lightweight multi-functional rabbit AVN model based on the Aliev-Panfilov two-variable cardiac cell model. The AVN model includes fast (FP) and slow (SP) pathways, primary pacemaking in the sinoatrial node, subsidiary pacemaking in the SP, and takes into account the asymmetry of coupling between model cells. At the same time, the model is accompanied by a visualization of electrical conduction in the AVN, revealing the interaction between SP and FP in the form of ladder diagrams. The AVN model demonstrates broad functionality, including normal sinus rhythm, AVN automaticity, filtering of high-rate atrial rhythms during atrial fibrillation and atrial flutter with Wenckebach periodicity, direction-dependent properties, and realistic anterograde and retrograde conduction curves in the control case and the cases of FP and SP ablation. To show the validity of the proposed model, we compare the simulation results with the available experimental data. Despite its simplicity, the proposed model can be used both as a stand-alone module and as a part of complex three-dimensional atrial or whole heart simulation systems and can help to understand some puzzling functions of AVN.
The plasma degradome reflects later development of NASH fibrosis after liver transplant
Authors: Li Jiang , Sato Toshifumi , Hernández-Tejero María , Beier Juliane I. , Sayed Khaled , Benos Panayiotis V , Wilkey Daniel W , Humar Abhinav , Merchant Michael L , Duarte-Rojo Andres , Arteel Gavin E 
Published: February 2023

AbstractAlthough liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease, and decreased survival. Lack of risk stratification strategies hamper liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., ‘degradome’) of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether inflammatory liver injury caused by post-LT NASH would yield a unique degradome profile, predictive of severe post-LT NASH fibrosis, we performed a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without). Total plasma peptides were isolated and analyzed by 1D-LC-MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. Qualitative and quantitative peptide features data were developed from MSn datasets using PEAKS Studio X (v10). LC-MS/MS yielded ∼2700 identifiable peptide features based on the results from Peaks Studio analysis. Several peptides were significantly altered in patients that later developed fibrosis and heatmap analysis of the top 25 most significantly-changed peptides, most of which were ECM-derived, clustered the 2 patient groups well. Supervised modeling of the dataset indicated that a fraction of the total peptide signal (∼15%) could explain the differences between the groups, indicating a strong potential for representative biomarker selection. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. Both The plasma degradome profile of post-LT patients yields stark difference based on later development of post-LT NASH fibrosis. This approach could yield new “fingerprints” that can serve as minimally-invasive biomarkers of negative outcomes post-LT.
Smartwatch-based prediction of single-stride and stride-to-stride gait outcomes using regression-based machine learning
Authors: Bailey Christopher A. , Mir-Orefice Alexandre , Uchida Thomas K. , Nantel Julie , Graham Ryan B. 
Published: February 2023

2.Abstract and key termsSpatiotemporal variability during gait is linked to fall risk and could be monitored using wearable sensors. Although many users prefer wrist-worn sensors, most applications position at other sites. We developed and evaluated an application using a consumer-grade smartwatch inertial measurement unit (IMU). Young adults (N = 41) completed seven-minute conditions of treadmill gait at three different speeds. Single-stride outcomes (stride time, length, width, and speed) and spatiotemporal variability (coefficient of variation of each single-stride outcome) were recorded using an optoelectronic system, while 232 single- and multi-stride IMU metrics were recorded using an Apple Watch Series 5. These metrics were input to train linear, ridge, support vector machine (SVM), random forest, and extreme gradient boosting (xGB) models of each spatiotemporal outcome. We conducted Model × Condition ANOVAs to explore model sensitivity to speed-related responses. xGB models were best for single-stride outcomes (relative mean absolute error [% error]: 7–11%; intraclass correlation coefficient [ICC2,1]: 0.60–0.86) and SVM models were best for spatiotemporal variability (% error: 18–22%; ICC2,1= 0.47–0.64). Spatiotemporal changes with speed were captured by these models (Condition: p < 0.00625). Results support the feasibility of monitoring multi-stride spatiotemporal parameters using a smartwatch IMU and machine learning.
Mesenchymal Stromal Cell secretome is affected by tissue source, donor age and sex
Authors: Turlo AJ , Hammond DE , Ramsbottom KA , Soul J , Gillen A , McDonald K , Peffers MJ , Clegg PD 
Published: February 2023

AbstractVariation in Mesenchymal Stromal Cell (MSC) function depending on their origin is problematic, as it may confound clinical outcomes of MSC therapy. Current evidence suggests that the therapeutic benefits of MSCs is primarily attributed to secretion of various biologically active factors (secretome). However, the effect of donor characteristics on the MSC secretome composition remains largely unknown. Here, we examined the influence of donor age, sex and tissue source, on the protein profile of the equine MSC secretome. Initially, we used dynamic metabolic labelling with stable isotopes combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify secreted proteins in MSC conditioned media (CM). Seventy proteins were classified as classically-secreted based on the rate of isotope label incorporation into newly synthesised proteins released into the extracellular space. Next, we analysed CM of bone marrow- (n = 14) and adipose-derived MSCs (n = 16) with label-free LC-MS/MS proteomics. Clustering analysis of 314 proteins detected across all samples identified tissue source as the main factor driving variability in MSC CM proteomes. Linear modelling applied to the subset of 70 secreted proteins identified tissue-related difference in the abundance of 23 proteins. There was an age-related decrease in the abundance of two proteins (CTHRC1, LOX), which has been validated with western blot and enzymatic activity assay. There was limited evidence of sex-related differences in protein abundance. In conclusion, this study provides evidence that tissue source and donor age contribute to heterogeneity in the protein composition of MSC secretomes which may influence the effects of MSC-based cell therapy.Significance statementThis research shows for the first time that donor age can influence the proteins secreted by mesenchymal stromal cells (MSC), which is considered the main mechanism through which they mediate their biological actions. This information may improve our understanding of the variable outcomes observed in MSC clinical studies, as well as identify optimal sources and donor selection for specific clinical applications.
Genetic diversity and population structure ofEpichloefungal pathogens of plants in natural ecosystems
Authors: Treindl Artemis D. , Stapley Jessica , Leuchtmann Adrian 
Published: February 2023

AbstractUnderstanding the population genetic processes driving the evolution of plant pathogens is of central interest to plant pathologists and evolutionary biologists alike. However, most studies focus on host-pathogen associations in agricultural systems of high genetic and environmental homogeneity and less is known about the genetic structure of pathogen populations infecting wild plants in natural ecosystems. We performed parallel population sampling of two pathogenicEpichloespecies occurring sympatrically on different host grasses in natural and seminatural grasslands in Europe:E. typhinainfectingDactylis glomerataandE. clarkiiinfectingHolcus lanatus. We sequenced 422 haploid isolates and generated genome-wide SNP datasets to investigate genetic diversity and population structure. In both species geographically separated populations formed genetically distinct groups, however population separation was less distinct inE. typhinacompared toE. clarkii. The patterns of among population admixture also differed between species across the same geographic range: we found higher levels of population genetic differentiation and a stronger effect of isolation by distance inE. clarkiicompared toE. typhina, consistent with lower levels of gene flow in the former. This pattern may be explained by the different dispersal abilities of the two pathogens and is expected to be influenced by the genetic structure of host populations. In addition, genetic diversity was higher inE. typhinapopulations compared toE. clarkii, indicative of higher effective population size inE. typhina. These results suggest that the effect of genetic drift and the efficacy of selection may differ in the two species. Our study provides evidence of how ecologically similar species occupying the same geographical space can experience different evolutionary contexts, which could influence local adaptation and coevolutionary dynamics of these fungal pathogens.
Simultaneous Knockouts of the Oxytocin and Vasopressin 1b Receptors in Hippocampal CA2 Impair Social Memory
Authors: Cymerblit-Sabba Adi , Walsh Caroline , Duan Kai-Zheng , Song June , Holmes Oliver , Young W. Scott 
Published: February 2023

AbstractOxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. The oxytocin (Oxtr) and vasopressin 1b (Avpr1b) receptors are co-expressed in the pyramidal neurons of the hippocampal subfield CA2 and are known to play a critical role in social memory formation. How the neuropeptides perform this function in this region is not fully understood. Here, we report the behavioral effects of a life-long conditional removal (knockout, KO) of either the Oxtr alone or both Avpr1b and Oxtr from the pyramidal neurons of CA2 as well as the resultant changes in synaptic transmission within the different fields of the hippocampus. Surprisingly, the removal of both receptors results in mice that are unable to habituate to a familiar female presented for short duration over short intervals but are able to recognize and discriminate females when presented for a longer duration over a longer interval. Importantly, these double KO mice were unable to discriminate between a male littermate and a novel male. Synaptic transmission between CA3 and CA2 is enhanced in these mice, suggesting a compensatory mechanism is activated to make up for the loss of the receptors. Overall, our results demonstrate that co-expression of the receptors in CA2 is necessary to allow intact social memory processing.
Genomic vulnerability to climate change and mutation load are affected by past declines in effective population size in two sedentary arctic bird species
Authors: Rödin-Mörch Patrik , Squires Theodore , Magnússon Kristinn P. , Höglund Jacob 
Published: February 2023

AbstractUsing whole genome re-sequencing data we study the effects of climate influenced declines in effective population size on the accumulation of deleterious mutations and the response to future climate change in populations of cold-adapted avian sister species from the Holarctic: rock ptarmigan (Lagopus muta) and willow ptarmigan (Lagopus lagopus). We reconstruct the demographic histories of the populations and determine their nucleotide diversity, past and present inbreeding, and mutation load. Genomic vulnerability to future climate change scenarios (also known as offset) is predicted for the populations.. We show that relatively small and isolated populations have reduced nucleotide diversity, higher signatures of past and present inbreeding, and higher estimates of mutation load. Among the studied populations, the most vulnerable to a mismatch between current and predicted future environments are rock ptarmigan populations in East Greenland, Iceland, and Svalbard, while among willow ptarmigan, subspecies residing on the British Isles are the most vulnerable.