bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DocMaps Framework for representing assertions on research products in an extensible, machine-readable, and discoverable format
Authors: McDowell Gary S. , Polka Jessica K. , Ross-Hellauer Tony , Stein Gabriel 
Published: July 2021

AbstractPeer review of a research product varies widely depending on the publishers and platforms involved in the process. As scholarly publishing is disrupted by new innovations, peer review processes become more heterogeneous, placing an increasing burden on the researcher in understanding how they can communicate their scholarship. New ways to model such processes, and increase transparency, trust, and experimentation in scholarly publishing are needed. Many are emerging but can tend to focus on the needs of creators, and not those of readers, funders, and the whole scholarly publishing ecosystem. They may not place focus on representing editorial practices in ways that can be reliably aggregated, surfaced, and queried; are often limited to traditional peer review processes; and cannot capture the full range of editorial practices and events needed to accommodate alternative publication, review, and curation models. To support researchers in a world of experimentation in scholarly publishing, we propose a machine-readable, extensible, and discoverable framework for representing and surfacing review and editorial processes. Working with a Technical Committee composed of interested parties by employing a modified Delphi Method, we developed initial guiding principles and proposals towards an object-level editorial metadata framework compatible with a broad range of possible futures for scholarly publishing. We present the results of this process with a proposal and example use cases for DocMaps, a framework for representing object-level assertions.
Palmitoylation targets the Calcineurin phosphatase to the Phosphatidylinositol 4-kinase complex at the plasma membrane
Authors: Ulengin-Talkish Idil , Parson Matthew AH , Jenkins Meredith L , Roy Jagoree , Shih Alexis ZL , St-Denis Nicole , Gulyas Gergo , Balla Tamas , Gingras Anne-Claude , Várnai Péter , Conibear Elizabeth , Burke John E , Cyert Martha S. 
Published: July 2021

AbstractCalcineurin, the conserved protein phosphatase and target of immunosuppressants, is a critical mediator of Ca2+ signaling. To discover novel calcineurin-regulated processes we examined an understudied isoform, CNAβ1. We show that unlike canonical cytosolic calcineurin, CNAβ1 localizes to the plasma membrane and Golgi due to palmitoylation of its divergent C-terminal tail, which is reversed by the ABHD17A depalmitoylase. Palmitoylation targets CNAβ1 to a distinct set of membrane-associated interactors including the phosphatidylinositol 4-kinase (PI4KA) complex containing EFR3B, PI4KA, TTC7B and FAM126A. Hydrogen-deuterium exchange reveals multiple calcineurin-PI4KA complex contacts, including a calcineurin-binding peptide motif in the disordered tail of FAM126A, which we establish as a calcineurin substrate. Calcineurin inhibitors decrease PI4P production during Gq-coupled GPCR signaling, suggesting that calcineurin dephosphorylates and promotes PI4KA complex activity. In sum, this work discovers a new calcineurin-regulated signaling pathway highlighting the PI4KA complex as a regulatory target and revealing that dynamic palmitoylation confers unique localization, substrate specificity and regulation to CNAβ1.
An analytical pipeline for DNA Methylation Array Biomarker Studies
Authors: Lu Jennifer , Korbie Darren , Trau Matt 
Published: July 2021

AbstractDNA methylation is one of the most commonly studied epigenetic biomarkers, due to its role in disease and development. The Illumina Infinium methylation arrays still remains the most common method to interrogate methylation across the human genome, due to its capabilities of screening over 480, 000 loci simultaneously. As such, initiatives such as The Cancer Genome Atlas (TCGA) have utilized this technology to examine the methylation profile of over 20,000 cancer samples. There is a growing body of methods for pre-processing, normalisation and analysis of array-based DNA methylation data. However, the shape and sampling distribution of probe-wise methylation that could influence the way data should be examined was rarely discussed. Therefore, this article introduces a pipeline that predicts the shape and distribution of normalised methylation patterns prior to selection of the most optimal inferential statistics screen for differential methylation. Additionally, we put forward an alternative pipeline, which employed feature selection, and demonstrate its ability to select for biomarkers with outstanding differences in methylation, which does not require the predetermination of the shape or distribution of the data of interest.AvailabilityThe Distribution test and the feature selection pipelines are available for download at: https://github.com/uqjlu8/DistributionTest
Twisting DNA by Salt
Authors: Cruz-León Sergio , Vanderlinden Willem , Müller Peter , Forster Tobias , Staudt Georgina , Lin Yi-Yun , Lipfert Jan , Schwierz Nadine 
Published: July 2021

AbstractThe structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of DNA- changes with concentration and identity of the surrounding ions. To resolve how cations influence the helical twist, we combine single-molecule magnetic tweezer experiments and extensive all- atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali and divalent alkaline earth cations. First, DNA twist increases monotonously with increasing concentration for all ions investigated. Second, for a given salt concentration, DNA twist strongly depends on cation identity. At 100 mM concentration, DNA twist increases as Ba2+ < Na+ < K+ < Rb+ < Li+ ≈ Cs+ < Sr2+ < Mg2+ < Ca2+. Our molecular dynamics simulations reveal that preferential binding of the cations to the DNA backbone or the nucleobases has opposing effects on DNA twist and provides the microscopic explanation of the observed ion specificity. However, the simulations also reveal shortcomings of existing force field parameters for Cs+ and Sr2+. The comprehensive view gained from our combined approach provides a foundation for understanding and predicting cation-induced structural changes both in nature and in DNA nanotechnology.
The (non) accuracy of mitochondrial genomes for family level phylogenetics: the case of erebid moths (Lepidoptera; Erebidae)
Authors: Ghanavi Hamid Reza , Twort Victoria , Hartman Tobias Joannes , Zahiri Reza , Wahlberg Niklas 
Published: July 2021

AbstractThe use of molecular data to study evolutionary history of different organisms, revolutionized the field of systematics. Now with the appearance of high throughput sequencing (HTS) technologies more and more genetic sequence data is available. One of the important sources of genetic data for phylogenetic analyses has been mitochondrial DNA. The limitations of mitochondrial DNA for the study of phylogenetic relationships have been thoroughly explored in the age of single locus phylogenies. Now with the appearance of genomic scale data, more and more mitochondrial genomes are available. Here we assemble 47 mitochondrial genomes using whole genome Illumina short reads of representatives of the family Erebidae (Lepidoptera), in order to evaluate the accuracy of mitochondrial genome application in resolving deep phylogenetic relationships. We find that mitogenomes are inadequate for resolving subfamily level relationships in Erebidae, but given good taxon sampling, we see its potential in resolving lower level phylogenetic relationships.
Reciprocal changes in voltage-gated potassium and subthreshold inward currents help maintain firing dynamics of AVPV kisspeptin neurons during the estrous cycle
Authors: Starrett J. Rudolph , DeFazio R. Anthony , Moenter Suzanne M. 
Published: July 2021

AbstractKisspeptin-expressing neurons in the anteroventral-periventricular nucleus (AVPV) are part of a neural circuit generating the gonadotropin-releasing hormone (GnRH) surge. This process is estradiol-dependent and occurs on the afternoon of proestrus in female mice. On proestrus, AVPV kisspeptin neurons express more kisspeptin and exhibit higher frequency action potentials and burst firing compared to diestrus, which is characterized by a pulsatile rather than a prolonged surge of GnRH secretion. We hypothesized changes in voltage-gated potassium conductances shape activity profiles of these cells in a cycle-dependent manner. Whole-cell voltage-clamp recordings of GFP-identified AVPV kisspeptin neurons in brain slices from diestrous and proestrous mice revealed three subcomponents of the voltage-sensitive K+ current: fast-inactivating, slow-inactivating, and residual. During proestrus, the V50 of inactivation of the fast-inactivating current was depolarized and the amplitude of the slow-inactivating component was reduced compared to diestrus; the residual component was consistent across both stages. Computational models were fit to experimental data, including published estrous-cycle effects on other voltage-gated currents. Computer simulations suggest proestrus-typical K+ currents are suppressive compared to diestrus. Interestingly, larger T-type, persistent-sodium, and hyperpolarization-activated currents during proestrus compensate for this suppressive effect while also enabling post-inhibitory rebound bursting. These findings suggest modulation of voltage-gated K+ and multiple subthreshold depolarizing currents across the negative to positive feedback transition maintain AVPV kisspeptin neuron excitability in response to depolarizing stimuli. These changes also enable firing in response to hyperpolarization, providing a net increase in neuronal excitability, which may contribute to activation of this population leading up to the preovulatory GnRH surge.Significance StatementGnRH neurons provide the central signal to initiate ovulation by releasing a surge of hormone. GnRH neurons are regulated by other cells including those expressing kisspeptin, a potent stimulator of GnRH secretion. Kisspeptin neurons in the anteroventral-periventricular nucleus (AVPV) express more kisspeptin and become more active during the afternoon of proestrus, the phase of the rodent estrous (reproductive) cycle when the GnRH surge occurs. We found voltage-dependent potassium currents in AVPV kisspeptin neurons change with phase of the estrous cycle. Firing simulations indicated these changes are suppressive if occurring in isolation. But proestrous-typical increases in subthreshold depolarizing currents overcome this suppression and promote greater excitability by increasing rebound firing, possibly contributing to the preovulatory activation of this system.
Partitioning gene-mediated disease heritability without eQTLs
Authors: Weiner Daniel J. , Gazal Steven , Robinson Elise B. , O’Connor Luke J. 
Published: July 2021

AbstractUnknown SNP-to-gene regulatory architecture complicates efforts to link noncoding GWAS associations with genes implicated by sequencing or functional studies. eQTLs are used to link SNPs to genes, but expression in bulk tissue explains a small fraction of disease heritability. A simple but successful approach has been to link SNPs with nearby genes, but the fraction of heritability mediated by these genes is unclear, and gene-proximal (vs. gene-mediated) heritability enrichments are attenuated accordingly. We propose the Abstract Mediation Model (AMM) to estimate (1) the fraction of heritability mediated by the closest or kth-closest gene to each SNP and (2) the mediated heritability enrichment of a gene set (e.g. genes with rare-variant associations). AMM jointly estimates these quantities by matching the decay in SNP enrichment with distance from genes in the gene set. Across 47 complex traits and diseases, we estimate that the closest gene to each SNP mediates 27% (SE: 6%) of heritability, and that a substantial fraction is mediated by genes outside the ten closest. Mendelian disease genes are strongly enriched for common-variant heritability; for example, just 21 dyslipidemia genes mediate 25% of LDL heritability (211x enrichment, P = 0.01). Among brain-related traits, genes involved in neurodevelopmental disorders are only about 4x enriched, but gene expression patterns are highly informative, with detectable differences in per-gene heritability even among weakly brain-expressed genes.
An information theoretic method to resolve millisecond-scale spike timing precision in a comprehensive motor program
Authors: Putney Joy , Niebur Tobias , Conn Rachel , Sponberg Simon 
Published: July 2021

AbstractSensory inputs in nervous systems are often encoded at the millisecond scale in a temporally precise code. There is now a growing appreciation for the prevalence of precise timing encoding in motor systems. Animals from moths to birds control motor outputs using precise spike timing, but we largely do not know at what scale timing matters in these circuits due to the difficulty of recording a complete set of spike-resolved motor signals and relatively few methods for assessing spike timing precision. We introduce a method to estimate spike timing precision in motor circuits using continuous MI estimation at increasing levels of added uniform noise. This method can assess spike timing precision at fine scales for encoding rich motor output variation. We demonstrate the advantages of this approach compared to a previously established discrete information theoretic method of assessing spike timing precision. We use this method to analyze a data set of simultaneous turning (yaw) torque output and EMG recordings from the 10 primary muscles ofManduca sextaas tethered moths visually tracked a robotic flower moving with a 1 Hz sinusoidal trajectory. We know that all 10 muscles in this motor program encode the majority of information about yaw torque in spike timings, but we do not know whether individual muscles receive information encoded at different levels of precision. Using the continuous MI method, we demonstrate that the scale of temporal precision in all motor units in this insect flight circuit is at the sub-millisecond or millisecond-scale, with variation in precision scale present between muscle types. This method can be applied broadly to estimate spike timing precision in sensory and motor circuits in both invertebrates and vertebrates.
The 4.4 Å structure of the giant Melbournevirus virion belonging to the Marseilleviridae family
Authors: Burton-Smith Raymond N. , Narayana Reddy Hemanth Kumar , Svenda Martin , Abergel Chantal , Okamoto Kenta , Murata Kazuyoshi 
Published: July 2021

SummaryMembers of Marseilleviridae, one family of icosahedral giant viruses classified in 2012 have been identified worldwide in all types of environments. The virion shows a characteristic internal membrane extrusion at the five-fold vertices of the capsid, but its structural details need to be elucidated. We now report the 4.4 Å cryo-electron microscopy structure of the Melbournevirus capsid. An atomic model of the major capsid protein (MCP) shows a unique cup structure on the trimer that accommodates additional proteins. A polyalanine model of the penton base protein shows internally extended N- and C-terminals, which indirectly connect to the internal membrane extrusion. The Marseilleviruses share the same orientational organisation of the MCPs as PBCV-1 and CroV, but do not appear to possess a protein akin to the “tape measure” of these viruses. Minor capsid proteins named PC-β, zipper, and scaffold are proposed to control the dimensions of the capsid during assembly.
Increased intestinal permeability in an orally-reactive peanut allergy model identifies Angiopoietin like-4 as a biomarker
Authors: Steinbach Erin C. , Smeekens Johanna M. , Roy Satyaki , Toyonaga Takahiko , Cornaby Caleb , Perini Layna , Berglind Ana , Kulis Michael D. , Kim Edwin H. , Ferris Martin T. , Furey Terrence S. , Burks A. Wesley , Sheikh Shehzad Z. 
Published: July 2021

AbstractPeanut allergy reaction severity correlates with increased intestinal epithelial cell (IEC) barrier permeability. CC027/GeniUnc mice develop peanut allergy by intragastric administration of peanut proteins without adjuvant. We report that peanut-allergic CC027/GeniUnc mice showed increased IEC barrier permeability and systemic peanut allergen Ara h 2 after challenge. Jejunal epithelial cell transcriptomics showed effects of peanut allergy on IEC proliferation, survival, and metabolism, and revealed IEC-predominant angiopoietin like-4 (Angptl4) as a unique feature of CC027/GeniUnc peanut allergy. CC027/GeniUnc mice and peanut-allergic pediatric patients demonstrated significantly higher serum Angptl4 and ANGPTL4 compared to control C3H/HeJ mice and non-peanut-allergic but atopic patients, respectively, highlighting its potential as a biomarker of peanut allergy.
Retinal ganglion cell-specific genetic regulation in primary open angle glaucoma
Authors: Daniszewski Maciej S. , Senabouth Anne , Liang Helena H. , Han Xikun , Lidgerwood Grace E. , Hernández Damián , Sivakumaran Priyadharshini , Clarke Jordan E. , Lim Shiang Y. , Lees Jarmon G. , Rooney Louise , Gulluyan Lerna , Souzeau Emmanuelle , Graham Stuart L. , Chan Chia-Ling , Nguyen Uyen , Farbehi Nona , Gnanasambandapillai Vikkitharan , McCloy Rachael A. , Clarke Linda , Kearns Lisa , Mackey David A , Craig Jamie E. , MacGregor Stuart , Powell Joseph E. , Pébay Alice , Hewitt Alex W. 
Published: July 2021

ABSTRACTTo assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared to those from healthy individuals. We performed single-cell RNA-sequencing of a total of 330,569 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 2,235 significant loci across all cell types, 58 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 54 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.
Population model of Temnothorax albipennis as a distributed dynamical system II: secret of “chemical reaction” in collective house-hunting in ant colonies is unveiled by operator methods
Authors: Qiu Siwei 
Published: July 2021

AbstractThe collective intelligence of animal groups is a complex algorithm for computer scientist and a many-body problem for physics of living system. We show how the time evolution of features in such a system, like number of ants in particular state for colonies, can be mapped to many-body problems in non-equilibrium statistical mechanics. There exist role transitions of active and passive ant between distributed functions, including exploration, assessing, recruiting and transportation in the house-hunting process. Theoretically, such a process can be approximately described as birth-death process where large number of particles living in the Fock space and particles of one sub-type transfer to a different sub-type with some probability. Started from the master equation with constrain of the quorum criterion, we express the evolution operator as a functional integral mapping from operators acting on Fock space in number representation to functional space in coherent state representation. We then read out the action from the evolution operator, and we use least action principal equations of motion, which are the number field equations. The equations we get are couple ordinary differential equations, which can faithfully describe the original master equation, and hence fully describe the system. This method provides us differential equation-based algorithm, which allow us explore parameter space with respect to more complicated agent-based algorithm. The algorithm also allows exploring stochastic process with memory in a Markovian way, which provide testable prediction on collective decision making.
Age-Related Changes in the Rhesus Macaque Eye
Authors: Lin Kira H. , Tran Tu , Kim Soohyun , Park Sangwan , Chen Jiajia , Timothy Stout J. , Chen Rui , Rogers Jeffrey , Yiu Glenn , Thomasy Sara , Moshiri Ala 
Published: July 2021

AbstractPurposeTo assess age-related changes in the rhesus macaque eye and evaluate them to corresponding human age-related eye disease.MethodsData from eye exams and imaging tests including intraocular pressure (IOP), lens thickness, axial length, and retinal optical coherence tomography (OCT) images were evaluated from 142 individuals and statistically analyzed for age-related changes. Quantitative autofluorescence (qAF) was measured as was the presence of macular lesions as related to age.ResultsAges of the 142 rhesus macaques ranged from 0.7 to 29 years (mean=16.4 years, stdev=7.5 years). Anterior segment measurements such as IOP, lens thickness, and axial length were acquired. Advanced retinal imaging in the form of optical coherence tomography and qAF were obtained. Quantitative assessments were made and variations by age groups were analyzed to compare with established age-related changes in human eyes. Quantitative analysis of data revealed age-related increase in intraocular pressure, ocular biometry (lens thickness and axial length), and presence of macular lesions. Age-related changes in thicknesses of retinal layers on OCT were observed and quantified. Age was correlated with increased qAF.ConclusionsThe rhesus macaque has age-related ocular changes similar to humans. IOP increases with age while retinal ganglion cell layer thickness decreases. Macular lesions develop in some aged animals. Our findings support the concept that rhesus macaques may be useful for the study of important age-related diseases such as glaucoma, macular diseases, and cone disorders, and for development of therapies for these diseases.