bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-read sequencing characterizes mitochondrial and plastid genome variants in Arabidopsismsh1mutants
Authors: Zou Yi , Zhu Weidong , Sloan Daniel B. , Wu Zhiqiang 
Published: March 2022

SummaryThe abundant repeats in plant mitochondrial genomes can cause rapid genome rearrangements and are also a major obstacle in short-read sequencing studies. Nuclear-encoded proteins such as MSH1 are known to suppress the generation of repeat-associated mitochondrial genome variants, but our understanding of these mechanisms has been constrained by the limitations of short-read technologies. Here, we used highly accurate long-read sequencing (PacBio HiFi) to characterize mitochondrial and plastid genome variants inArabidopsis thaliana msh1mutant individuals. The HiFi reads provided a global view of recombination dynamics with detailed quantification of parental and crossover recombination products for both large and small repeats. We found that recombination breakpoints were distributed relatively evenly across the length of repeated sequences and detected widespread internal exchanges of sequence variants between pairs of imperfect repeats in the mitochondrial genome ofmsh1mutants. Long-read assemblies of mitochondrial genomes from seven otherArabidopsis thalianawild-type accessions differed by repeat-mediated structural rearrangements similar to those observed inmsh1mutants, but they were all in a simple low-heteroplasmy state. TheArabidopsisplastid genome generally lacks small repeats and exhibited a very different pattern of variant accumulation inmsh1mutants compared with the mitochondrial genome. Our data illustrate the power of HiFi technology in studying repeat-mediated recombination in plant organellar genomes and improved the sequence resolution for recombinational processes suppressed by MSH1.SignificancePlant organellar genomes can undergo rapid rearrangements. Long-read sequencing provides a detailed and quantitative view of mitochondrial and plastid genome variants normally suppressed by MSH1, advancing our understanding of plant organellar genome dynamics.
Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy and improves prediction
Authors: Hindley Guy , Shadrin Alexey , der Meer Dennis van , Parker Nadine , Cheng Weiqiu , O’Connell Kevin S. , Bahrami Shahram , Lin Aihua , Karadag Naz , Holen Børge , Bjella Thomas , Fan Chun C , Ueland Torill , Djurovic Srdjan , Smeland Olav B. , Frei Oleksandr , Dale Anders M. , Andreassen Ole A. 
Published: March 2022

AbstractPersonality and cognition are heritable mental traits, and their genetic determinants may be distributed across interconnected brain functions. However, previous studies have employed univariate approaches which reduce complex traits to summary measures. We applied the “pleiotropy-informed” multivariate omnibus statistical test (MOSTest) to genome-wide association studies (GWAS) of 35 item and task-level measures of neuroticism and cognition from the UK Biobank (n=336,993). We identified 431 significant genetic loci and found evidence of abundant pleiotropy across personality and cognitive domains. Functional characterisation implicated genes with significant tissue-specific expression in all tested brain tissues and enriched in brain-specific gene-sets. We conditioned independent GWAS of the Big 5 personality traits and cognition on our multivariate findings, which boosted genetic discovery in other personality traits and improved polygenic prediction. These findings advance our understanding of the polygenic architecture of complex mental traits, indicating a prominence of pleiotropic genetic effects across higher-order domains of mental function.Graphical abstract
Identification of highly cross-reactive mimotopes for a public T cell response in murine melanoma
Authors: Grace Beth E. , Backlund Coralie M. , Morgan Duncan M. , Kang Byong H. , Singh Nishant K. , Huisman Brooke D. , Rappazzo C. Garrett , Moynihan Kelly D. , Maiorino Laura , Dobson Connor S. , Kyung Taeyoon , Gordon Khloe S. , Holec Patrick V. , Takou Mbah Overbeck C. , Garafola Daniel , Wu Shengwei , Love J. Christopher , Wittrup K. Dane , Irvine Darrell J. , Birnbaum Michael E. 
Published: March 2022

AbstractWhile immune checkpoint blockade results in durable responses for some patients, many others have not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently induce antigen-specific responses in a broadly applicable manner. Here, we characterized the CD8+T cell response to a murine model of melanoma following combination immunotherapy to determine the basis of tumor recognition. Sequencing of tumor-infiltrating T cells revealed a repertoire of highly homologous TCR sequences that were particularly expanded in treated mice and which recognized an antigen from an endogenous retrovirus. While vaccination against this peptide failed to raise a protective T cell responsein vivo, engineered antigen mimotopes induced a significant expansion of CD8+T cells cross-reactive to the original antigen. Vaccination with mimotopes resulted in killing of antigen-loaded cellsin vivoyet showed modest survival benefit in a prophylactic vaccine paradigm. Together, this work demonstrates the identification of a dominant tumor-associated antigen and generation of mimotopes which can induce robust functional T cell responses that are cross-reactive to the endogenous antigen across multiple individuals.
Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds
Authors: Boateng Samuel T. , Roy Tithi , Agbo Mercy E. , Banang-Mbeumi Sergette , Chamcheu Roxane-Cherille N. , Bramwell Marion , Pham Long K. , Jackson Keith E. , Hill Ronald A. , Nagalo Bolni Marius , Efimova Tatiana , Fotie Jean , Chamcheu Jean Christopher 
Published: March 2022

AbstractMelanoma and non-melanoma skin cancers are the most-lethal and commonest forms of skin cancers, that affecting one-fifth of the US population. With the aim of identifying new lead compounds as starting point for attaining cost-effective therapies, a small library of about 90 molecules was screenedin vitroagainst A375, SKMEL-28, A431, SCC-12 skin cancer cell lines. About 35 of them, mainly dihydroquinolines, C–C and C–N linked biphenyls, and substituted methylgallate or aniline derivatives, displayed low-micromolar range activities, primarily against the A431 and SCC-12 squamous carcinoma cell lines, with only a handful of these compounds displaying any activity against the A375 and SKMEL-28 melanoma cell lines. Compounds11(A431: IC50= 5.0 µM, SCC-12: IC50= 2.9 µM, SKMEL-28: IC50= 4.9 µM, A375: IC50= 6.7 µM) and13(A431: IC50= 5.0 µM, SCC-12: IC50= 3.3 µM, SKMEL-28: IC50= 13.8 µM, A375: IC50= 17.1 µM) were the most active across all these cell lines. Furthermore, many of the hit compounds showed little to no activity against mammalian nontumorigenic immortalized HaCaT cells, with a far better selectivity index than cisplatin (a well-known anticancer agent used as a positive control). Compounds11and13significantly and dose-dependently induced apoptosis of SCC-12 and SK-MEL-28 cells as evidenced by the downregulation of Bcl-2 and upregulation of Bax protein expression levels, and by cleaved caspase-3, caspase-9 and PARP levels. Both agents also significantly reduced scratch wound healing, colony formation, and activated expression levels of major cancer molecular targets such as RSK/AKT/ERK1/2 and S6K1. To provide a better attribute profile for each of the hit molecules, in-silico target(s) prediction, pharmacokinetic and ADMET studies are also reported, together with some preliminary structure-activity relationship outlines. The SwissTargetPrediction web-based tool identified CDK8, CLK4, nuclear receptor ROR, tyrosine protein-kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, as likely targets for these hit compounds. Furthermore, the SwissADME web_tool predicted these compounds to exhibit high GI tract absorption, good skin permeation, and a viable biodegradability profile. To summarize, these data highlight the promising anticancer potential of these small molecules leads, warranting further investigation and/or optimization towards obtaining clinical candidates for combatting both melanoma and non-melanoma skin cancers.
Greening conceals evergreening: contrasting trends for a socio-ecological system in Arctic Europe
Authors: Tuomi M.W. , Utsi T.Aa. , Yoccoz N.G. , Armstrong C.W. , Gonzalez V. , Hagen S.B. , Jónsdóttir I.S. , Pugnaire F.I. , Shea K. , Wardle D.A. , Zielosko S. , Bråthen K.A. 
Published: March 2022

AbstractOngoing Arctic greening can increase productivity and reindeer pasture quality in the tundra. However, greening may also entail proliferation of unpalatable species, with distinct consequences for pastoral socio-ecological systems (SES).We show extensive greening across 20 reindeer districts in northern Norway between 2003 and 2020. The allelopathic, evergreen dwarf-shrub crowberry biomass increased by 60%, contrasted by smaller increases of deciduous dwarf-shrubs and stagnating forb and graminoid biomass.We found evidence, although uncertain, of a negative relationship between biomass and reindeer densities, but only among forbs, the least abundant plant group.Our results challenge the management decision-making, which aims at sustainable pasture management, but which assumes stationary density-dependent relationships. Changes in temporal vs. spatial relationships should be included as management criteria, to avoid mismanaging a SES in transition.Large-scale shift towards increased allelopathy may undermine the resource base of a key Arctic herbivore and pastoral SES.
Genome-wide association and genomic prediction of resistance to Flavobacterium columnare in a farmed rainbow trout population
Authors: Fraslin Clémence , Koskinen Heikki , Nousianen Antti , Houston Ross D. , Kause Antti 
Published: March 2022

AbstractColumnaris disease is an emerging disease affecting farmed rainbow trout (Oncorhynchus mykiss) globally. In aquaculture breeding, genomic selection has been increasingly used to improve traits that are difficult to measure on candidate fish (such as disease resistance traits). Following a natural outbreak of columnaris disease, 3,054 exposed fish and their 81 parents (33 dams and 48 sires) were genotyped with the 57K SNP Axiom™ trout genotyping array. Genetic parameters of host resistance (measured as a binary survival trait) were estimated, a genome wide association study was performed, and the accuracy of pedigree-based and genomic prediction was estimated. After quality controls, 2,874 challenged fish (1,403 dead fish and 1,471 alive fish) and 78 parents genotyped for 27,907 SNPs remained. Pedigree based heritability was estimated to be 0.18 and 0.35 on the observed and underlying scale, respectively. Genomic heritability was estimated to be 0.21 and 0.43 on the observed and underlying scale, respectively. A quantitative trait loci (QTL) was detected on chromosome Omy3, significant at the genome-wide level, along with several suggestive QTLs on two other chromosomes. The additive effect on mortality proportion of the peak SNP from Omy3 was estimated to be 0.11 (0.018; se). Pedigree-based prediction accuracy was 0.59, and the use of genomic evaluation increased the prediction accuracy by at least 13.6%. Using the second iteration of a weighted genomic-based evaluation increased the prediction accuracy by 18.6% compared to the pedigree-based model. These results suggest that resistance is a suitable target trait for genetic improvement by selective breeding, and genomic selection may be a useful approach to speed up this process.
Regulation strategies for two-output biomolecular networks
Authors: Alexis Emmanouil , Schulte Carolin CM , Cardelli Luca , Papachristodoulou Antonis 
Published: March 2022

AbstractFeedback control theory facilitates the development of self-regulating systems with desired performance which are predictable and insensitive to disturbances. Feedback regulatory topologies are found in many natural systems and have been of key importance in the design of reliable synthetic bio-devices operating in complex biological environments. Here, we study control schemes for biomolecular processes with two outputs of interest, expanding previous traditional concepts describing one-output systems. Regulation of such processes may unlock new design possibilities but can be challenging due to coupling interactions; also potential disturbances applied on one of the outputs may affect both. We therefore propose architectures for robustly manipulating the ratio and linear combinations of the outputs as well as each of the outputs independently. To demonstrate their characteristics, we apply these architectures to a simple process of two mutually activated biomolecular species. We also highlight the potential for experimental implementation by exploring synthetic realizations bothin vivoandin vitro. This work presents an important step forward in building bio-devices capable of sophisticated functions.
IFT20 governs mesenchymal stem cell fate through positively regulating TGF-β-Smad2/3-Glut1 signaling mediated glucose metabolism
Authors: Li Yang , Yang Shuting , Liu Yang , Qin Ling , Yang Shuying 
Published: March 2022

AbstractAberrant lineage allocation of mesenchymal stem cells (MSCs) could cause bone marrow osteoblast-adipocyte imbalance, and glucose as an important nutrient is required for the maintenance of the MSCs’ fate and function. Intraflagellar transport 20 (IFT20) is one of the IFT complex B protein which regulates osteoblast differentiation, and bone formation, but how IFT20 regulates MSCs’ fate remains undefined. Here, we demonstrated that IFT20 controls MSC lineage allocation through regulating glucose metabolism during skeletal development. IFT20 deficiency in the early stage of MSCs caused significantly shortened limbs, decreased bone mass and significant increase in marrow fat. However, deletion of IFT20 in the later stage of MSCs and osteocytes just slightly decreased bone mass and bone growth and increased marrow fat. Additionally, we found that loss of IFT20 in MSCs promotes adipocyte formation, which enhances RANKL expression and bone resorption. Conversely, ablation of IFT20 in adipocytes reversed these phenotypes. Mechanistically, loss of IFT20 in MSCs significantly decreased glucose tolerance and suppressed glucose uptake and lactate and ATP production. Moreover, loss of IFT20 significantly inhibited TGF-β-Smad2/3 signaling and decreased the binding activity of Smad2/3 toGlut1promoter to downregulate Glut1 expression. These findings indicate that IFT20 plays essential roles for preventing MSC lineage allocation into adipocytes through controlling TGF-β-Smad2/3-Glut1 mediated glucose metabolism.
In vivo chromatic and spatial tuning of foveolar retinal ganglion cells in Macaca fascicularis
Authors: Godat Tyler , Cottaris Nicolas P. , Patterson Sara , Kohout Kendall , Parkins Keith , Yang Qiang , Strazzeri Jennifer M. , McGregor Juliette E. , Brainard David H. , Merigan William H. , Williams David R. 
Published: March 2022

AbstractThe primate fovea is specialized for high acuity chromatic vision, with the highest density of cone photoreceptors and a disproportionately large representation in visual cortex. The unique visual properties conferred by the fovea are conveyed to the brain by retinal ganglion cells, the somas of which lie at the margin of the foveal pit. Microelectrode recordings of these centermost retinal ganglion cells have been challenging due to the fragility of the fovea in the excised retina. Here we overcome this challenge by combining high resolution fluorescence adaptive optics ophthalmoscopy with calcium imaging to optically record functional responses of foveal retinal ganglion cells in the living eye. We use this approach to study the chromatic responses and spatial transfer functions of retinal ganglion cells using spatially uniform fields modulated in different directions in color space and monochromatic drifting gratings. We recorded from over 350 cells across three Macaca fascicularis primates over a time period of weeks to months. We find that the majority of the L vs. M cone opponent cells serving the most central foveolar cones have spatial transfer functions that peak at high spatial frequencies (20-40 c/deg), reflecting strong surround inhibition that sacrifices sensitivity at low spatial frequencies but preserves the transmission of fine detail in the retinal image. In addition, we fit to the drifting grating data a detailed model of how ganglion cell responses draw on the cone mosaic to derive receptive field properties of L vs. M cone opponent cells at the very center of the foveola. The fits are consistent with the hypothesis that foveal midget ganglion cells are specialized to preserve information at the resolution of the cone mosaic. By characterizing the functional properties of retinal ganglion cells in vivo through adaptive optics, we characterize the response characteristics of these cells in situ.
Genomic analyses identify biological processes and functions between M1 and M2 macrophages
Authors: Chang Tingxiang , Zhang Tingting , Gu Hanming , Wang Jing 
Published: March 2022

AbstractMacrophages can be induced by a variety of factors to change their phenotype and functions. M1 and M2 macrophages play converse roles during inflammation or other diseases. However, the mechanism and function of M1 and M2 macrophages are still not clear. This study aims to identify the different molecules and functions by analyzing the RNA-seq data. The GSE189354 was created by the Illumina HiSeq 4000 (Mus musculus). The KEGG and GO analyses indicated the Phagosome and Hematopoietic cell lineage are the major biological processes between M1 and M2 macrophages. Moreover, we further identified ten molecules including Il6, Il1b, Tlr2, Myc, Fn1, Itgax, Cxcl10, Ccl5, Cxcr4, and Pparg. Therefore, our study may provide novel knowledge of innate immunity.
Cytologic Scoring of Equine Exercise-Induced Pulmonary Hemorrhage (EIPH): Performance of Human Experts and a Deep Learning-Based Algorithm
Authors: Bertram Christof A. , Marzahl Christian , Bartel Alexander , Stayt Jason , Bonsembiante Federico , Beeler-Marfisi Janet , Barton Ann K. , Brocca Ginevra , Gelain Maria E. , Gläsel Agnes , Preez Kelly du , Weiler Kristina , Weissenbacher-Lang Christiane , Breininger Katharina , Aubreville Marc , Maier Andreas , Klopfleisch Robert , Hill Jenny 
Published: March 2022

AbstractExercise-induced pulmonary hemorrhage (EIPH) is a relevant respiratory disease in sport horses which can be diagnosed by examination of bronchoalveolar lavage fluid (BALF) cells using the total hemosiderin score (THS). The aim of this study was to evaluate the diagnostic accuracy and reproducibility of trained annotators and to validate a deep learning-based algorithm for the THS. Digitized, iron-stained cytological specimens were prepared from 52 equine BALF samples. Ten annotators produced a THS for each slide according to published methods. The reference methods for comparing annotator’s and algorithmic performance included a ground truth dataset, the mean annotators’ THSs, and chemical iron measurements. Results of the study showed that annotators had marked inter-observer variability of the THS, which was mostly due to a systematic error between annotators in grading the intracytoplasmatic hemosiderin content of individual macrophages. Regarding overall measurement error between the annotators, 87.7% of the variance of the could be reduced by using standardized grades based on the ground truth. The algorithm was highly consistent with the ground truth in assigning hemosiderin grades. Compared to the ground truth THS, annotators had an accuracy of diagnosing EIPH (THS of < or ≥ 75) of 75.7% whereas the algorithm had an accuracy of 92.3% with no marked difference in correlation to chemical iron measurements. The results show that deep learning-based algorithms are useful for improving reproducibility and routine applicability of the THS. For THS by experts, a diagnostic uncertainty interval of 40 to 110 is proposed. THSs within this interval have insufficient reproducibility regarding the EIPH diagnosis.
A functional trait approach reveals the effects of landscape context on ecosystem services provided by urban birds
Authors: Swartz Timothy M. , Gleditsch Jason M. , Behm Jocelyn E. 
Published: March 2022

AbstractLand use intensification in urban areas can have profound effects on biological communities that provide valuable ecosystem services to urban residents. We used a functional response and effect trait approach to determine how bird species’ responses to local and landscape-scale habitat of urban green spaces affects the supply of cultural and regulating ecosystem services. We sampled bird communities and habitat variables in urban green spaces that varied in local and landscape-scale habitat composition and compiled a dataset of species’ response and effect traits related to nesting, foraging, diet, and visual and acoustic aesthetic appeal. Overall, the landscape-scale context of a green space had a stronger influence on species’ abundances than local-scale habitat. Landscape-scale impervious surface surrounding our study sites interacted with response traits related to nesting in human-built structures, clutch size, and consumption of invertebrates to drive bird species’ abundances. Because correlations between response and effect traits can influence the effect traits available to provide ecosystem services at a site, we explored the correlation of these three response traits to a suite of effect traits and found the response traits were correlated with several effect traits related to diet and regulating services but correlated with few of the plumage and acoustic traits that produce cultural services. Finally, we found that effect traits associated with cultural and regulating ecosystem services varied strongly along the landscape-scale gradient of urbanization. Sites with high impervious surface cover are expected to have low levels of invertebrate pest control and visual appeal but high levels of acoustic appeal, diet evenness (generalism), and granivory. Overall, our study highlights the key role of landscape-scale habitat in driving bird-mediated ecosystem services and underscores the importance of regional urban planning to create healthy and livable cities.
Using Biometric Data to Measure and Predict Emotional Engagement of Video Games
Authors: Vazquez Janette , Abdelrahman Samir , Wasden Chris , Jardine Stuart , Judd Colby , Davis Matthew , Facelli Julio C. 
Published: March 2022

AbstractMeasurement and prediction of engagement in video games are very important because these are indicators to guide the development of game applications. Existing methods to predict game engagement are mostly based on subjective evaluations. This paper presents results correlating subjective and biometric data to show the potential of using biometric measures for assessment and prediction of engagement. Using three different games, we measured the biometric responses of participants and analyzed the responses using statistical and data mining methods. We compared the results with those obtained using subjective evaluations. Our results show that biometric measurements do correlate with subjective measures and better predict the self-reported engagement of a game.