bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term temporal stability of Northeast Arctic cod (Gadus morhua) otolith morphology
Authors: Denechaud Côme , Smoliński Szymon , Geffen Audrey J , Godiksen Jane A 
Published: January 2020

Abstract
Otolith shape analysis provides a robust tool for the discrimination of many fish stocks in the context of fisheries management. However, there has been little research to examine within-stock temporal stability of otolith morphology in relation to changes in the environment and stock conditions. This study investigated the variability of Northeast Arctic (NEA) cod (Gadus morhua) otolith shape between 1933 and 2015, using elliptical Fourier descriptors extracted from archived material of 2968 mature fish. Series of hierarchical multivariate models were developed to relate shape to the identified optimal windows of some environmental drivers. Differences between years accounted for &lt;3% of the observed variation and no significant differences were found between the average cohort shapes. The models not only confirmed that fish growth was the strongest driver of shape differences, but also highlighted effects of temperature and biomass-related variables at different life stages. Extrinsic factors described only a small fraction of the observed variance, which indicates that environmental changes over time likely account for less than the natural inter-individual variability in otolith shape. These results suggest that overall shape remains relatively stable through time within NEA cod, which further contributes towards a consensus on the biological interpretation of shape differences.
Recent Out-of-Africa Migration of Human Herpes Simplex Viruses
Authors: Forni Diego , Pontremoli Chiara , Clerici Mario , Pozzoli Uberto , Cagliani Rachele , Sironi Manuela 
Published: January 2020

AbstractHerpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplex viruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations have limited geographic structure and the most evident clustering by geography is likely due to recent bottlenecks. For HSV-2, the only level of population structure is accounted for by the so-called “worldwide” and “African” lineages. Analysis of ancestry components and nucleotide diversity, however, did not support the view that the worldwide lineage followed early humans during out-of-Africa dispersal. Although phylogeographic analysis confirmed an African origin for both viruses, molecular dating with a method that corrects for the time-dependent rate phenomenon indicated that HSV-1 and HSV-2 migrated from Africa in relatively recent times. In particular, we estimated that the HSV-2 worldwide lineage left the continent in the 18th century, which corresponds to the height of the transatlantic slave trade, possibly explaining the high prevalence of HSV-2 in the Americas (second highest after Africa). The limited geographic clustering of HSV-1 makes it difficult to date its exit from Africa. The split between the basal clade, containing mostly African sequences, and all other strains was dated at ∼5,000 years ago. Our data do not imply that herpes simplex viruses did not infect early humans but show that the worldwide distribution of circulating strains is the result of relatively recent events.
Rubella Vaccine Persistence Within Cutaneous Granulomas in Common Variable Immunodeficiency Disorder
Authors: Bender Nicole R. , Cardwell Leah A. , Siegel Dawn , Sokumbi Olayemi 
Published: January 2020

Abstract:
Common variable immunodeficiency disorder is a primary immunodeficiency disorder characterized by reduced levels of serum immunoglobulins and impaired antibody response. This condition may be associated with development of noninfectious granulomatous dermatitis of the skin which may be disfiguring and destructive. There are no published guidelines for the treatment of cutaneous granulomas in this patient population. In recent studies, rubella virus–positive cells in granulomas were localized to M2 macrophages which have an important role in wound healing and the secretion of immunoregulatory cytokines. We present a case of treatment-refractory, disfiguring common variable immunodeficiency disorder–associated granulomatous dermatitis. Immunofluorescence microscopy of the biopsy specimen confirmed the presence of rubella vaccine capsid proteins in M2 macrophages within the granuloma, a newly recognized phenomenon in this patient population. This knowledge may serve to identify future therapeutic targets or preventative strategies for granulomatous dermatitis in patients with primary immunodeficiency disorder.
Management of Wilson Disease Diagnosed in Infancy
Authors: Valentino Pamela L. , Roberts Eve A. , Beer Stacey , Miloh Tamir , Arnon Ronen , Vittorio Jennifer M. , Schilsky Michael L. 
Published: January 2020

ABSTRACTIncreased access to molecular genetic testing is changing the demographics for diagnosing inherited disorders and imposing new challenges for medical management. Wilson disease (WD), typically diagnosed in older children and adults, can now be detected in utero and in infants (children younger than 24 months, including neonates) via genetic testing. An evidence‐based approach to management of these neonates and extremely young children, who are typically asymptomatic, has been hampered by lack of clinical experience. We present a case of an infantile diagnosis of WD, review available experience, and discuss current trends in antenatal genetic testing of parents and fetus that may lead to a very early diagnosis of WD. Based on physiological and nutritional considerations, we propose an algorithmic approach to management of infantile WD as a starting point for further discussion. Future collaboration amongst specialists is essential to identify evidence‐based approaches and best practice for managing treatment of infants with genetically diagnosed WD.
Open‐label Phase 3 Continuation Study of Cholic Acid in Patients With Inborn Errors of Bile Acid Synthesis
Authors: Heubi James E. , Setchell Kenneth D.R. 
Published: January 2020

ABSTRACTBackground:In patients with bile acid synthesis disorders (BASD), impairment in the primary bile acid synthetic pathway leads to reduced primary bile acids, upregulated synthesis of cholesterol, and production and accumulation of hepatotoxic atypical bile acids. Primary bile acid therapy downregulates bile acid synthesis, reduces the production of hepatotoxic intermediates, and produces a functional bile acid pool fostering normal liver function.Methods:This phase 3, open‐label, single‐arm study included patients with BASD who had received cholic acid (10–15 mg · kg−1 · day−1) as part of a previous study, or were newly diagnosed. Efficacy assessments included urinary atypical bile acids; serum liver chemistries; body weight and height. Efficacy analyses compared baseline with worst postbaseline response (primary) or best postbaseline response (sensitivity). Treatment‐emergent adverse events (TEAEs) were summarized.Results:Of 53 total patients (single enzyme defects, n = 41; Zellweger spectrum disorders, n = 12), 22 (42%) were treatment‐naïve, and 31 (58%) were on cholic acid from a previous study. Mean age at diagnosis was 55 months, and at present study, baseline was 9 years. Using baseline‐to‐best postbaseline analyses, statistically significant improvements in urinary bile acids (P = 0.003), height (P < 0.001), and body weight (P < 0.001) were observed. Serum alanine aminotransferase and aspartate aminotransferase levels tended to decrease from baseline in treatment‐naïve patients following cholic acid treatment and remained stable in previously treated patients. Treatment‐naïve patients improved in all baseline‐to‐best postbaseline analyses. The most common TEAE was upper respiratory tract infection (17%).Conclusion:Oral cholic acid provides a safe and efficacious short‐ and long‐term therapy for patients with BASD.
MetaConnect, a new platform for population viability modelling to assist decision makers in conservation and urban planning
Authors: Moulherat Sylvain , Bestion Elvire , Baguette Michel , Moulherat Matthieu , Palmer Stephen C.F. , Travis Justin M.J. , Clobert Jean 
Published: January 2020

AbstractIn a context of global change, scientists and policy-makers require tools to address the issue of biodiversity loss. Population viability analysis (PVA) has been the main tool to deal with this problem. However, the tools developed during the 90s poorly integrate recent scientific advances in landscape genetics and dispersal. We developed a flexible and modular modelling platform for PVA that addresses many of the limitations of existing software. MetaConnect is an individual-based, process-based and PVA-oriented modelling platform which could be used as a research or a decision-making tool. Here, we present the core base modelling of MetaConnect. We demonstrate its potential use through a case study illustrating the platform’s capability for performing integrated PVA including extinction probability estimation, genetic differentiation and landscape connectivity analysis. We used MetaConnect to assess the impact of infrastructure works on the natterjack toad metapopulation functioning.
FFselect: An improved linear mixed model for genome-wide association study in populations featuring shared environments confounded by relatedness
Authors: Schultz Nichol , Weigel Kent 
Published: January 2020

AbstractLinear mixed models are effective tools to identify genetic loci contributing to phenotypic variation while handling confounding due to population structure and cryptic relatedness. Recent improvements of the linear mixed model for genome-wide association analysis have been directed at more accurately modeling loci of large effect. We describe FFselect (https://github.com/NicholSchultz/FFselect), a novel method that both builds upon recent advances and further extends the linear mixed model for genome-wide association analysis to allow modeling of shared environmental effects. FFselect improves power, controls false discovery rate, and simultaneously corrects for environmental confounding to improve the utility of GWAS.
Spatial Proximity Moderates Genotype Uncertainty in Genetic Tagging Studies
Authors: Augustine Ben C. , Royle J. Andrew , Linden Daniel W. , Fuller Angela K. 
Published: January 2020

AbstractAccelerating declines of an increasing number of animal populations worldwide necessitate methods to reliably and efficiently estimate demographic parameters such as population density and trajectory. Standard methods for estimating demographic parameters from noninvasive genetic samples are inefficient because lower quality samples cannot be used, and they do not allow for errors in individual identification. We introduce the Genotype Spatial Partial Identity Model (SPIM), which integrates a genetic classification model with a spatial population model to combine both spatial and genetic information, thus reducing genotype uncertainty and increasing the precision of demographic parameter estimates. We apply this model to data from a study of fishers (Pekania pennanti) in which 37% of samples were originally discarded because of uncertainty in individual identity. The Genotype SPIM density estimate using all collected samples was 25% more precise than the original density estimate, and the model identified and corrected 3 errors in the original individual identity assignments. A simulation study demonstrated that our model increased the accuracy and precision of density estimates 63% and 42%, respectively, using 3 PCRs per genetic sample. Further, the simulations showed that the Genotype SPIM model parameters are identifiable with only one PCR per sample, and that accuracy and precision are relatively insensitive to the number of PCRs for high quality samples. Current genotyping protocols devote the majority of resources to replicating and confirming high quality samples, but when using the Genotype SPIM, genotyping protocols could be more efficient by devoting more resources to low quality samples.SignificanceWe present a new statistical framework for the estimation of animal demographic parameters, such as abundance, density, and growth rate, from noninvasive genetic samples (e.g., hair, scat). By integrating a genetic classification model with a spatial population model, we show that accounting for spatial proximity of samples reduces genotype uncertainty and improves parameter estimation. Our method produces a fundamentally different approach to genetic capture-recapture by sharing information between the normally disjunct steps of assigning individual identities to genetic samples and modeling population processes. Further, it leads to more efficient protocols for processing genetic samples, which can lower project costs and expand opportunities for applying noninvasive genetics to conservation and management problems.
Overcoming Genetic Drop-outs in Variants-based Lineage Tracing from Single-cell RNA Sequencing Data
Authors: Lu Tianshi , Park Seongoh , Zhu James , Zhan Xiaowei , Wang Xinlei , Zhu Hao , Wang Tao 
Published: January 2020

ABSTRACTLineage tracing provides key insights into the fates of individual cells in complex tissues. Recent works on lineage reconstruction based on the single-cell expression data are suitable for short time frames while tracing lineage based on more stable genetic markers is needed for studies that span time scales over months or years. However, variant calling from the single-cell RNA sequencing (scRNA-Seq) data suffers from “genetic drop-outs”, including low coverage and allelic bias, which presents significant obstacles for lineage reconstruction. Prior studies focused only on mitochondrial (chrM) variants and need to be expanded to the whole genome to capture more variants with clearer physiological meaning. However, non-chrM variants suffer even more severe drop-outs than chrM variants, although drop-outs affect all variants. We developed strategies to overcome genetic drop-outs in scRNA-Seq-derived whole genomic variants for accurate lineage tracing, and we developed SClineger, a Bayesian Hierarchical model, to implement our approach. Our validation analyses on a series of sequencing protocols demonstrated the necessity of correction for genetic drop-outs and consideration of variants in the whole genome, and also showed the improvement that our approach provided. We showed that genetic-based lineage tracing is applicable for single-cell studies of both tumors and non-tumor tissues using our approach, and can reveal novel biological insights not afforded by expressional analyses. Interestingly, we showed that cells of various lineages grew under the spatial constraints of their respective organs during the developmental process. Overall, our work provides a powerful tool that can be applied to the large amounts of already existing scRNA-Seq data to construct the lineage histories of cells and derive new knowledge.
Label-free three-dimensional observations and quantitative characterisation of on-chip vasculogenesis using optical diffraction tomography
Authors: Lee Chungha , Kim Seunggyu , Hugonnet Herve , Lee Moosung , Park Weisun , Jeon Jessie S. , Park YongKeun 
Published: January 2020

AbstractLabel-free, three-dimensional (3D) quantitative observations of on-chip vasculogenesis were achieved using optical diffraction tomography. Exploiting 3D refractive index maps as an intrinsic imaging contrast, the vascular structures, multicellular activities, and subcellular organelles of endothelial cells were imaged and analysed throughout vasculogenesis to characterise mature vascular networks without exogenous labelling.Abstract Figure
LocusFocus: A web-based colocalization tool for the annotation and functional follow-up of GWAS
Authors: Panjwani Naim , Wang Fan , Wang Cheng , He Gengming , Mastromatteo Scott , Bao Allen , Gong Jiafen , Rommens Johanna M , Sun Lei , Strug Lisa J 
Published: January 2020

AbstractGenome-wide association studies (GWAS) have primarily identified trait-associated loci in the non-coding genome. Colocalization analyses of SNP-level associations from GWAS with expression quantitative trait loci (eQTL) evidence enable the generation of hypotheses about responsible mechanism, genes and tissues of origin to guide functional characterization. Here, we present a web-based colocalization browsing and testing tool named LocusFocus (https://locusfocus.research.sickkids.ca). LocusFocus formally tests colocalization using our establishedSimple Summethod to identify the most relevant genes and tissues for a particular GWAS locus in the presence of high linkage disequilibrium and/or allelic heterogeneity. Full documentation and source code for LocusFocus are publicly available.
SMRT sequencing yields the chromosome-scale reference genome of tea tree,Camellia sinensisvar.sinensis
Authors: Zhang Qun-Jie , Li Wei , Li Kui , Nan Hong , Shi Cong , Zhang Yun , Dai Zhang-Yan , Lin Yang-Lei , Yang Xiao-Lan , Tong Yan , Zhang Dan , Lu Cui , Wang Chen-feng , Liu Xiao-xin , Jiang Wen-Kai , Wang Xing-Hua , Zhang Xing-Cai , Liu Zhong-Hua , Eichler Evan E. , Gao Li-Zhi 
Published: January 2020

AbstractTea is the oldest and most popular nonalcoholic beverage consumed in the world. It provides abundant secondary metabolites that account for its diverse flavors and health benefits. Here we present the first high-quality chromosome-length reference genome ofC. sinensisvar.sinensisusing long read single-molecule real time (SMRT) sequencing and Hi-C technologies to anchor the ∼2.85-Gb genome assembly into 15 pseudo-chromosomes with a scaffold N50 length of ∼195.68 Mb. We annotated at least 2.17 Gb (∼74.13%) of repetitive sequences and high-confidence prediction of 40,812 protein-coding genes in the ∼2.92-Gb genome assembly. This accurately assembled genome allows us to comprehensively annotate functionally important gene families such as those involved in the biosynthesis of catechins, theanine and caffeine. The contiguous genome assembly provides the first view of the repetitive landscape allowing us to accurately characterize retrotransposon diversity. The large tea tree genome is dominated by a handful of Ty3-gypsylong terminal repeat (LTR) retrotransposon families that recently expanded to high copy numbers. We uncover the latest bursts of numerous non-autonomous LTR retrotransposons that may interfere with the propagation of autonomous retroelements. This reference genome sequence will largely facilitate the improvement of agronomically important traits relevant to the tea quality and production.
Chamaeleo: a robust library for DNA storage coding schemes
Authors: Ping Zhi , Zhang Haoling , Chen Shihong , Zhuang Qianlong , Zhu Sha Joe , Shen Yue 
Published: January 2020

AbstractChamaeleo is currently the only collection library that focuses on adapting multiple well-established coding schemes for DNA storage. It provides a tool for researchers to study various coding schemes and apply them in practice. Chamaeleo adheres to the concept of high aggregation and low coupling for software design which will enhance the performance efficiency. Here, we describe the working pipeline of Chamaeleo, and demonstrate its advantages over the implementation of existing single coding schemes. The source code is available athttps://github.com/ntpz870817/Chamaeleo, it can be also installed by the command of pip.exe, “pip install chamaeleo”. Alternatively, the wheel file can be downloaded athttps://pypi.org/project/Chamaeleo/. Detailed documentation is available athttps://chamaeleo.readthedocs.io/en/latest/.Author SummaryDNA is now considered to be a promising candidate media for future digital information storage in order to tackle the global issue of data explosion. Transcoding between binary digital data and quanternary DNA information is one of the most important steps in the whole process of DNA digital storage. Although several coding schemes have been reported, researchers are still investigating better strategies. Moreover, the scripts of these coding schemes use different programming languages, software architectures and optimization contents. Therefore, we here introduce Chamaeleo, a library in which several classical coding schemes are collected, to reconstruct and optimize them. One of the key features of this tool is that we modulize the functions and make it feasible for more customized way of usage. Meanwhile, developers can also incorporate their new algorithms according to the framework expediently. Based on the benchmark tests we conducted, Chamaeleo shows better flexibility and expandability compared to original packages and we hope that it will help the further study and applications in DNA digital storage.
The Arabidopsis N-terminal Acetyltransferase NAA50 Regulates Plant Growth and Defense
Authors: Neubauer Matthew , Innes Roger W. 
Published: January 2020

AbstractStress signaling in plants is carefully regulated to ensure proper development and reproductive fitness. Overactive defense signaling can result in dwarfism as well as developmental defects. In addition to requiring a significant amount of energy, plant stress responses place a burden upon the cellular machinery, which can result in the accumulation of misfolded proteins and endoplasmic reticulum (ER) stress. Negative regulators of stress signaling, such asEDR1, ensure that stress responses are properly suspended when they are not needed. Here, we describe the role of an uncharacterized N-terminal acetyltransferase, NAA50, in the regulation of plant development and stress responses. Our results demonstrate that NAA50, an interactor of EDR1, plays an important role in regulating the tradeoff between plant growth and defense. Plants lackingNAA50display severe developmental defects as well as induced stress responses. Reduction ofNAA50expression results in arrested stem and root growth and senescence. Furthermore, our results demonstrate thatEDR1andNAA50are required for suppression of ER stress signaling. This work establishes thatNAA50is essential for plant development and the suppression of stress responses, likely through the regulation of ER stress. These experiments demonstrate a role for N-terminal acetylation in the suppression of ER stress, as well as the tradeoff between stress responses and development.One Sentence SummaryKnockout in Arabidopsis of the broadly conserved N-terminal acetyl transferase NAA50 induces ER stress, leading to severe dwarfism and induction of defense responses.