bluuebunny/crossref_metadata_2025_split huggingface dataset:
The unresolved phylogenomic tree of butterflies and moths (Lepidoptera): assessing the potential causes and consequences
Authors: Rota Jadranka , Twort Victoria , Chiocchio Andrea , Peña Carlos , Wheat Christopher W. , Kaila Lauri , Wahlberg Niklas 
Published: April 2021

AbstractThe field of molecular phylogenetics is being revolutionised with next-generation sequencing technologies making it possible to sequence large numbers of genomes for non-model organisms ushering us into the era of phylogenomics. The current challenge is no longer how to get enough data, but rather how to analyse the data and how to assess the support for the inferred phylogeny. We focus on one of the largest animal groups on the planet – butterflies and moths (order Lepidoptera). We clearly demonstrate that there are unresolved issues in the inferred phylogenetic relationships of the major lineages, despite several recent phylogenomic studies of the group. We assess the potential causes and consequences of the conflicting phylogenetic hypotheses. With a dataset consisting of 331 protein-coding genes and the alignment length over 290 000 base pairs, including 200 taxa representing 81% of lepidopteran superfamilies, we compare phylogenetic hypotheses inferred from amino acid and nucleotide alignments. The resulting two phylogenies are discordant, especially with respect to the placement of the superfamily Gelechioidea, which is likely due to compositional bias of both the nucleotide and amino acid sequences. With a series of analyses, we dissect our dataset and demonstrate that there is sufficient phylogenetic signal to resolve much of the lepidopteran tree of life. Overall, the results from the nucleotide alignment are more robust to the various perturbations of the data that we carried out. However, the lack of support for much of the backbone within Ditrysia makes the current butterfly and moth tree of life still unresolved. We conclude that taxon sampling remains an issue even in phylogenomic analyses, and recommend that poorly sampled highly diverse groups, such as Gelechioidea in Lepidoptera, should receive extra attention in the future.
Improving estimation of species distribution from citizen-science records
using data-integration models
Authors: Zulian Viviane , Miller David A. W. , Ferraz Gonçalo 
Published: April 2021

Abstract
Mapping species distributions is a crucial but challenging requirement of
wildlife management. The frequent need to sample vast expanses of potential
habitat increases the cost of planned surveys and rewards accumulation of
opportunistic observations. In this paper, we integrate planned survey data from
roost counts with opportunistic samples from eBird, WikiAves and Xeno-canto
citizen-science platforms to map the geographic range of the endangered
Vinaceous-breasted Parrot. We demonstrate the estimation and mapping of species
occurrence based on data integration while accounting for specifics of each data
set, including observation technique and uncertainty about the observations. Our
analysis illustrates 1) the incorporation of sampling effort, spatial
autocorrelation, and site covariates in a joint-likelihood, hierarchical,
data-integration model; 2) the evaluation of the contribution of each data set,
as well as the contribution of effort covariates, spatial autocorrelation, and
site covariates to the predictive ability of fitted models using a
cross-validation approach; and 3) how spatial representation of the latent
occupancy state (i.e. realized occupancy) helps identify areas with high
uncertainty that should be prioritized in future field work. Our results reveal
a Vinaceous-breasted Parrot geographic range of 434,670
km2, which is three times larger than the ‘Extant’ area
previously reported in the IUCN Red List. The exclusion of one data set at a
time from the analyses always resulted in worse predictions by the models of
truncated data than by the full model, which included all data sets. Likewise,
exclusion of spatial autocorrelation, site covariates, or sampling effort
resulted in worse predictions. The integration of different data sets into one
joint-likelihood model produced a more reliable representation of the species
range than any individual data set taken on its own improving the use of citizen
science data in combination with planned survey results.
Direct and indirect cues can enable dual-adaptation, but through different learning processes
Authors: Forano Marion , Schween Raphael , Taylor Jordan A. , Hegele Mathias , Franklin David W. 
Published: April 2021

AbstractSwitching between motor tasks requires accurate adjustments for changes in dynamics (grasping a cup) or sensorimotor transformations (moving a computer mouse). Dual-adaptation studies have investigated how learning of context-dependent dynamics or transformations is enabled by sensory cues. However, certain cues, such as color, have shown mixed results. We propose that these mixed results may arise from two major classes of cues: “direct” cues, which are part of the dynamic state and “indirect” cues, which are not. We hypothesized that explicit strategies would primarily account for adaptation for an indirect color cue but would be limited to simple tasks while a direct visual separation cue would allow implicit adaptation regardless of task complexity. To test this idea, we investigated the relative contribution of implicit and explicit learning in relation to contextual cue type (colored or visually shifted workspace) and task complexity (one or eight targets) in a dual-adaptation task. We found that the visual workspace location cue enabled adaptation across conditions primarily through implicit adaptation. In contrast, we found that the color cue was largely ineffective for dual-adaptation, except in a small subset of participants who appeared to use explicit strategies. Our study suggests that the previously inconclusive role of color cues in dual-adaptation may be explained by differential contribution of explicit strategies across conditions.New & NoteworthyWe present evidence that learning of context-dependent dynamics proceeds via different processes depending on the type of sensory cue used to signal the context. Visual workspace location enabled learning different dynamics implicitly, presumably because it directly enters the dynamic state estimate. In contrast, a color cue was only successful where learners were apparently able to leverage explicit strategies to account for changed dynamics. This suggests a unification for the previously inconclusive role of color cues.
The dual nature of metacommunity variability
Authors: Lamy Thomas , Wisnoski Nathan I. , Andrade Riley , Castorani Max C.N. , Compagnoni Aldo , Lany Nina , Marazzi Luca , Record Sydne , Swan Christopher M. , Tonkin Jonathan D. , Voelker Nicole , Wang Shaopeng , Zarnetske Phoebe L. , Sokol Eric R. 
Published: April 2021

AbstractThere is increasing interest in measuring ecological stability to understand how communities and ecosystems respond to broad-scale global changes. One of the most common approaches is to quantify the variation through time in community or ecosystem aggregate attributes (e.g., total biomass), referred to as aggregate variability. It is now widely recognized that aggregate variability represents only one aspect of communities and ecosystems, and compositional variability, the changes in the relative frequency of species in an assemblage, is equally important. Recent contributions have also begun to explore ecological stability at regional spatial scales, where interconnected local communities form metacommunities, a key concept in managing complex landscapes. However, the conceptual frameworks and measures of ecological stability in space have only focused on aggregate variability, leaving a conceptual gap. Here, we address this gap with a novel framework for quantifying the aggregate and compositional variability of communities and ecosystems through space and time. We demonstrate that the compositional variability of a metacommunity depends on the degree of spatial synchrony in compositional trajectories among local communities. We then provide a conceptual framework in which compositional variability of (i) the metacommunity through time and (ii) among local communities combine into four archetype scenarios:spatial stasis(low/low);spatial synchrony(high/low);spatial asynchrony(high/high) andspatial compensation(low/high). We illustrate this framework based on numerical examples and a case study of a macroalgal metacommunity in which low spatial synchrony reduced variability in aggregate biomass at the metacommunity scale, while masking high spatial synchrony in compositional trajectories among local communities. Finally, we discuss the role of dispersal, environmental heterogeneity, species interactions and suggest future avenues. We believe this framework will be helpful for considering both aspects of variability simultaneously which is important to better understand ecological stability in natural and complex landscapes in response to environmental changes.
The Hepcidin Regulator Erythroferrone is a New Member of the Erythropoiesis–Iron–Bone Circuitry
Authors: Castro-Mollo Melanie , Gera Sakshi , Martinez Marc Ruiz , Feola Maria , Gumerova Anisa , Planoutene Marina , Clementelli Cara , Sangkhae Veena , Casu Carla , Kim Se-Min , Ostland Vaughn , Han Huiling , Nemeth Elizabeta , Fleming Robert , Rivella Stefano , Lizneva Daria , Yuen Tony , Zaidi Mone , Ginzburg Yelena Z. 
Published: April 2021

ABSTRACTErythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression.Erfe-/-mice display low–bone–mass arising from increased bone resorption despite a concomitant increase in bone formation. Consistently,Erfe-/-osteoblasts exhibit enhanced mineralization,SostandRanklexpression, and BMP–mediated signalingex vivo. The ERFE effect on osteoclasts is mediated through increased osteoblastic RANKL and sclerostin expression, increasing osteoclastogenesis inErfe-/-mice. Importantly,Erfeloss in β–thalassemic (Hbbth3/+) mice, a disease model with increased ERFE expression, triggers profound osteoclastic bone resorption and bone loss. Together, ERFE exerts an osteoprotective effect by modulating BMP signaling in osteoblasts, decreasing RANKL production to limit osteoclastogenesis, and prevents excessive bone loss during expanded erythropoiesis in β–thalassemia.
Insm1-expressing neurons and secretory cells develop from a common pool of progenitors in the sea anemoneNematostella vectensis
Authors: Tournière Océane , Busengdal Henriette , Gahan James M. , Rentzsch Fabian 
Published: April 2021

ABSTRACTNeurons are highly specialized cells present in nearly all animals, but their evolutionary origin and relationship to other cell types is not well understood. We use here the sea anemoneNematostella vectensisas a model system for early-branching animals to gain fresh insights into the evolutionary history of neurons. We generated a transgenic reporter line to show that the transcription factorNvInsm1is expressed in post-mitotic cells that give rise to various types of neurons and secretory cells. Expression analyses, double transgenics and gene knockdown experiments show that theNvInsm1-expressing neurons and secretory cells derive from a common pool ofNvSoxB(2)-positive progenitor cells. These findings, together with the requirement forInsm1for the development of neurons and endocrine cells in vertebrates, support a close evolutionary relationship of neurons and secretory cells.
Improved data sets and evaluation methods for the automatic prediction of DNA-binding proteins
Authors: Zaitzeff Alexander , Leiby Nicholas , Motta Francis C. , Haase Steven B. , Singer Jedediah M. 
Published: April 2021

AbstractMotivationAccurate automatic annotation of protein function relies on both innovative models and robust datasets. Due to their importance in biological processes, the identification of DNA-binding proteins directly from protein sequence has been the focus of many studies. However, the data sets used to train and evaluate these methods have suffered from substantial flaws. We describe some of the weaknesses of the data sets used in previous DNA-binding protein literature and provide several new data sets addressing these problems. We suggest new evaluative benchmark tasks that more realistically assess real-world performance for protein annotation models. We propose a simple new model for the prediction of DNA-binding proteins and compare its performance on the improved data sets to two previously published models. Additionally, we provide extensive tests showing how the best models predict across taxonomies.ResultsOur new gradient boosting model, which uses features derived from a published protein language model, outperforms the earlier models. Perhaps surprisingly, so does a baseline nearest neighbor model using BLAST percent identity. We evaluate the sensitivity of these models to perturbations of DNA-binding regions and control regions of protein sequences. The successful data-driven models learn to focus on DNA-binding regions. When predicting across taxonomies, the best models are highly accurate across species in the same kingdom and can provide some information when predicting across kingdoms.Code and Data AvailabilityAll the code and data for this paper can be found athttps://github.com/AZaitzeff/tools_for_dna_binding_proteins.Contactalexander.zaitzeff@twosixtech.com
Loss ofUsp22enhances histone H2B monoubiquitination and stimulates intracellular and systemic interferon immunity
Authors: Dietlein Nikolaus , Wang Xi , Correa Esther Rodríguez , Erbil Beyza , Lipka Daniel B. , Begus-Nahrmann Yvonne , Kosinsky Robyn Laura , Johnsen Steven A. , Winkler Thomas H. , Rodewald Hans-Reimer 
Published: April 2021

AbstractInterferons protect from virus infections by inducing hundreds of interferon-stimulated genes (ISG) which orchestrate anti-viral adaptive and innate immunity. Upon viral infection or type I interferon (IFN) stimulation of cell lines, a histone modification, monoubiquitinated histone 2B (H2Bub1), increases at ISG loci, raising the possibility that a specific chromatin state can broadly stimulate IFN immunity in vivo. Here we show that, in the absence of virus infection or elevated interferon levels, mice lacking the relevant deubiquitinase,Usp22, in immune cells have elevated H2Bub1 levels. Hypermonoubiquitinated H2B is physically associated with dozens of ISG loci, and expression of large numbers of ISG is upregulated. This epigenetic state promotes intracellular and systemic immune phenotypes akin to adaptive and innate interferon immunity, and thereby identifiesUsp22as a negative regulator of interferon immunity.
High-quality genome and methylomes illustrate features underlying evolutionary success of oaks
Authors: Sork Victoria L. , Cokus Shawn J. , Fitz-Gibbon Sorel T. , Zimin Aleksey V. , Puiu Daniela , Garcia Jesse A. , Gugger Paul F. , Henriquez Claudia L. , Zhen Ying , Lohmueller Kirk E. , Pellegrini Matteo , Salzberg Steven L. 
Published: April 2021

AbstractThe genusQuercus, which emerged ~55 million years ago during globally warm temperatures, diversified into ~450 species. We present a high-qualityde novogenome assembly of a California endemic oak,Quercus lobata, revealing features consistent with oak evolutionary success. Effective population size remained large throughout history despite declining since the early Miocene. Analysis of 39,373 mapped protein-coding genes outlined copious duplications consistent with genetic and phenotypic diversity, both by retention of genes created during the ancientγwhole genome hexaploid duplication event and by tandem duplication within families, including the numerous resistance genes and also unexpected candidate genes for an incompatibility system involving multiple non-self-recognition genes. An additional surprising finding is that subcontext-specific patterns of DNA methylation associated with transposable elements reveal broadly-distributed heterochromatin in intergenic regions, similar to grasses (another highly successful taxon). Collectively, these features promote genetic and phenotypic variation that would facilitate adaptability to changing environments.
Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds
Authors: Smith Quinton , Chen Christopher , Bhatia Sangeeta 
Published: April 2021

ABSTRACTPatients with Alagille syndrome carry monogenic mutations in the Notch signaling pathway and face complications such as jaundice and cholestasis. Given the presence of intrahepatic ductopenia in these patients, Notch2 receptor signaling has been implicated in driving normal biliary development and downstream branching morphogenesis. As a result,in vitromodel systems of liver epithelium are needed to further mechanistic insight of biliary tissue assembly. Here, we systematically evaluate primary human intrahepatic cholangiocytes as a candidate population for such a platform and describe conditions that direct their branching morphogenesis. We find that extracellular matrix presentation, coupled with mitogen stimulation, promotes biliary branching in a Notch-dependent manner. These results demonstrate the utility of using 3D scaffolds for mechanistic investigation of cholangiocyte branching and provides a gateway to integrate biliary architecture in additionalin vitromodels of liver tissue.
GEM-DeCan: Improved tumor immune microenvironment profiling through novel gene expression and DNA methylation signatures predicts immunotherapy response
Authors: Xie Ting , Solórzano Jacobo , Madrid-Mencía Miguel , Essabbar Abdelmounim , Pernet Julien , Kuo Mei-Shiue , Hucteau Alexis , Coullomb Alexis , Verstraete Nina , Delfour Olivier , Cruzalegui Francisco , Pancaldi Vera 
Published: April 2021

AbstractQuantifying the proportion of the different cell types present in tumor biopsies remains a priority in cancer research. So far, a number of deconvolution methods have emerged for estimating cell composition using reference signatures, either based on gene expression or on DNA methylation from purified cells. These two deconvolution approaches could be complementary to each other, leading to even more performant signatures, in cases where both data types are available. However, the potential relationship between signatures based on gene expression and those based on DNA methylation remains underexplored.Here we present five new deconvolution signature matrices, based RNAseq data or on DNA methylation, which can estimate the proportion of immune cells and cancer cells in a tumour sample. We test these signature matrices on available datasets for in-silico and in-vitro mixtures, peripheral blood, cancer samples from TCGA, and a single-cell melanoma dataset. Cell proportions estimates based on deconvolution performed using our signature matrices, implemented within the EpiDISH framework, show comparable or better correlation with FACS measurements of immune cell-type abundance and with various estimates of cancer sample purity and composition than existing methods.Using publicly available data of 3D chromatin structure in haematopoietic cells, we expanded the list of genes to be included in the RNAseq signature matrices by considering the presence of methylated CpGs in gene promoters or in genomic regions which are in 3D contact with these promoters. Our expanded signature matrices have improved performance compared to our initial RNAseq signature matrix. Finally, we show the value of our signatures in predicting patient response to immune checkpoint inhibitors in three melanoma cancer cohorts, based on bulk tumour sample gene expression.We also provide GEM-DeCan: a snakemake pipeline, able to run an analysis from raw sequencing data to deconvolution based on various gene expression signature matrices, both for bulk RNASeq and DNA methylation data.
TBX5 drivesAldh1a2expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development
Authors: Rankin Scott A. , Steimle Jeffrey D. , Yang Xinan H. , Rydeen Ariel B. , Agarwal Kunal , Chaturvedi Praneet , Ikegami Kohta , Herriges Michael J. , Moskowitz Ivan P. , Zorn Aaron M. 
Published: April 2021

ABSTRACTThe gene regulatory networks that coordinate the development of the cardiac and pulmonary systems are essential for terrestrial life but poorly understood. The T-box transcription factor Tbx5 is critical for both pulmonary specification and heart development, but how these activities are mechanistically integrated remains unclear. We show thatTbx5regulates an evolutionarily conserved retinoic acid (RA)-Hedgehog-Wnt signaling cascade coordinating cardiopulmonary development. We demonstrate that Tbx5 directly maintains expression of the RA-synthesizing enzymeAldh1a2in the foregut lateral plate mesoderm via an intronic enhancer that is evolutionarily conserved among terrestrial vertebrates.Tbx5promotes posterior second heart field identity in a positive feedback loop with RA, antagonizing a Fgf8-Cyp regulatory module and restricting FGF activity to the anterior. Tbx5/Aldh1a2-dependent RA signaling also directly activatesShhtranscription in the adjacent foregut endoderm through the conserved MACS1 enhancer. Epithelial Hedgehog then signals back to the mesoderm, where together with Tbx5 it activates expression ofWnt2/2bthat ultimately induce pulmonary fate in the foregut endoderm. These results provide mechanistic insight into the interrelationship between heart and lung development informing cardiopulmonary evolution and birth defects.KEY FINDINGSTbx5 regulates second heart field patterning and pulmonary development via retinoic acid (RA) and Hedgehog (Hh) signaling.Tbx5 directly maintains transcription of the RA-synthesizing enzymeAldh1a2in the posterior second heart field mesoderm via an evolutionarily conserved intronic enhancer.Downstream of Tbx5, RA directly promotesShhtranscription through the evolutionarily conserved MACS1 endoderm enhancer.Downstream of Tbx5, RA suppresses FGF signaling to pattern the second heart field while promoting a Hedgehog-Wnt2/2b signaling cascade that induces pulmonary fate.SUMMARY STATEMENTTbx5-dependent Retinoic Acid signaling regulates an evolutionarily conserved gene regulatory network that coordinates cardiac and pulmonary development.
Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections
Authors: Ahrends Tomasz , Aydin Begüm , Matheis Fanny , Classon Cajsa , Furtado Gláucia C. , Lira Sérgio A. , Mucida Daniel 
Published: April 2021

AbstractThe enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss and dysmotility during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via β2-adrenergic receptors (β2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and -13 by eosinophils, which induced arginase-expressing MMs that prevented neuronal loss from an unrelated infection located in a different intestinal region. Collectively, these data suggest that distinct enteric pathogens trigger a state of disease- or tissue tolerance that preserves ENS number and functionality.