bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scalable method for estimating the regional polygenicity of complex traits
Authors: Johnson Ruth , Burch Kathryn S. , Hou Kangcheng , Paciuc Mario , Pasaniuc Bogdan , Sankararaman Sriram 
Published: January 2020

AbstractA key question in human genetics is understanding the proportion of SNPs modulating a particular phenotype or the proportion of susceptibility SNPs for a disease, termedpolygenicity. Previous studies have observed that complex traits tend to be highly polygenic, opposing the previous belief that only a handful of SNPs contribute to a trait. Beyond these genome-wide estimates, the distribution of polygenicity across genomic regions as well as the genomic factors that affect regional polygenicity remain poorly understood. A reason for this gap is that methods for estimating polygenicity utilize SNP effect sizes from GWAS. However, estimating regional polygenicity from GWAS effect sizes involves untangling the correlation between SNPs due to LD, leading to intractable computations for even a small number of SNPs. In this work, we propose a scalable method, BEAVR, to estimate the regional polygenicity of a trait given marginal effect sizes from GWAS and LD information. We implement a Gibbs sampler to estimate the posterior distribution of the regional polygenicity and derive a fast, algorithmic update to circumvent the computational bottlenecks associated with LD. The runtime of our algorithm is 𝒪(MK) forMSNPs andKsusceptibility SNPs, where the number of susceptibility SNPs is typicallyK≪M. By modeling the full LD structure, we show that BEAVR provides unbiased estimates of polygenicity compared to previous methods that only partially model LD. Finally, we show how estimates of regional polygenicity for BMI, eczema, and high cholesterol provide insight into the regional genetic architecture of each trait.
Single-Cell Electrophysiological Measurements Reveal Bacterial Membrane Potential Dynamics during Extracellular Electron Transfer
Authors: Pirbadian Sahand , Chavez Marko S. , El-Naggar Mohamed Y. 
Published: January 2020

AbstractExtracellular electron transfer (EET) allows microorganisms to gain energy by linking intracellular reactions to external surfaces ranging from natural minerals to the electrodes of bioelectrochemical renewable energy technologies. In the past two decades, electrochemical techniques have been used to investigate EET in a wide range of microbes, with emphasis on dissimilatory metal-reducing bacteria, such asShewanella oneidensisMR-1, as model organisms. However, due to the typically bulk nature of these techniques, they are unable to reveal the subpopulation variation in EET or link the observed electrochemical currents to energy gain by individual cells, thus overlooking the potentially complex spatial patterns of activity in bioelectrochemical systems. Here, to address these limitations, we use the cell membrane potential as a bioenergetic indicator of EET byS. oneidensisMR-1 cells. Using a fluorescent membrane potential indicator duringin vivosingle-cell level fluorescence microscopy in a bioelectrochemical reactor, we demonstrate that membrane potential strongly correlates with the electrode potential, produced current, and position of cells relative to the electrodes. The high spatial and temporal resolution of the reported technique can be used to study the single-cell level dynamics of EET not only on electrode surfaces, but also during respiration of other solid-phase electron acceptors.
mosaicFlye: Resolving long mosaic repeats using long error-prone reads
Authors: Bankevich Anton , Pevzner Pavel 
Published: January 2020

AbstractLong-read technologies revolutionized genome assembly and enabled resolution ofbridged repeats(i.e., repeats that are spanned by some reads) in various genomes. However, the problem of resolvingunbridged repeats(such as long segmental duplications in the human genome) remains largely unsolved, making it a major obstacle towards achieving the goal of complete genome assemblies. Moreover, the challenge of resolving unbridged repeats is not limited to eukaryotic genomes but also impairs assemblies of bacterial genomes and metagenomes. We describe the mosaicFlye algorithm for resolving complex unbridged repeats based on differences between various repeat copies and show how it improves assemblies of the human genome as well as bacterial genomes and metagenomes. In particular, we show that mosaicFlye results in a complete assembly of both arms of the human chromosome 6.
Novel phylogeny of angiosperms inferred from whole-genome microsynteny analysis
Authors: Zhao Tao , Xue Jiayu , Kao Shu-min , Li Zhen , Zwaenepoel Arthur , Schranz M. Eric , Van de Peer Yves 
Published: January 2020

AbstractDespite the wealth of genomic and transcriptomic data of pivotal angiosperm species, the phylogenetic relationships of flowering plants are still not fully resolved. Microsynteny, or the conservation of relative gene order, has been recognized as a valuable and alternative phylogenetic character to sequence-based characters (nucleotides or amino acids). Here, we present a novel approach for phylogenetic tree reconstruction based on genome-wide synteny network data. We generated and analyzed synteny networks from 123 species from 52 families across 31 orders of flowering plants, including several lineages for which phylogenetic relationships are ambiguous. We obtained a stable and highly resolved phylogeny that is largely congruent with sequence-based phylogenies. However, our results unveiled several novel relationships for some key clades, such as magnoliids sister to monocots, Vitales as sister to core-eudicots, and Saxifragales sister to Santalales, in turn both sister to Caryophyllales. Our results highlight that phylogenies based on genome structure and organization are complementary to sequence-based phylogenies and provide alternative hypotheses of angiosperm relationships to be further tested.
Simple and efficient measurement of transcription initiation and transcript levels with STRIPE-seq
Authors: Policastro Robert A. , Raborn R. Taylor , Brendel Volker P. , Zentner Gabriel E. 
Published: January 2020

AbstractAccurate mapping of transcription start sites (TSSs) is key for understanding transcriptional regulation. However, current protocols for genome-wide TSS profiling are laborious and/or expensive. We present Survey of TRanscription Initiation at Promoter Elements with high-throughput sequencing (STRIPE-seq), a simple, rapid, and cost-effective protocol for sequencing capped RNA 5’ ends from as little as 50 ng total RNA. Including depletion of uncapped RNA and SPRI bead cleanups, a STRIPE-seq library can be constructed in about five hours. We demonstrate application of STRIPE-seq to TSS profiling in yeast and human cells and show that it can also be effectively used for measuring transcript levels and differential gene expression analysis. In conjunction with our ready-to-use computational analysis workflows, STRIPE-seq is a straightforward, efficient means by which to probe the landscape of transcriptional initiation.
Cold exposure distinctively modulates parathyroid and thyroid hormones in cold-acclimatized and non-acclimatized humans
Authors: Kovaničová Zuzana , Kurdiová Tímea , Baláž Miroslav , Štefanička Patrik , Varga Lukáš , Kulterer Oana C. , Betz Matthias J. , Haug Alexander R. , Burger Irene A. , Kiefer Florian W. , Wolfrum Christian , Ukropcová Barbara , Ukropec Jozef 
Published: January 2020

AbstractContextCold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood.ObjectiveTo investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans.DesignCross-sectional study examining acute response to ice-water swimming and to experimental non-shivering thermogenesis (NST) induction in individuals acclimatized and non-acclimatized to cold. Seasonal variation in energy metabolism of ice-water swimmers and associations between circulating PTH and molecular components of thermogenic program in brown adipose tissue (BAT) of neck-surgery patients were evaluated.SettingClinical Research Center.Patients, ParticipantsIce-water swimmers (winter swim n=15, NST-induction n=6), non-acclimatized volunteers (NST-induction, n=11, elective neck surgery n = 36).Main Outcomes and ResultsIn ice-water swimmers, PTH and TSH increased in response to 15min winter swim, while activation of NST failed to regulate PTH and lowered TSH. In non-acclimatized men, NST-induction decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT 18F-FDG uptake was found across the two populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively withUCP1/UCP1,PPARGC1AandDIO2in BAT from neck surgery patients.ConclusionsRegulation of PTH and thyroid hormones during cold exposure in humans depends on the cold acclimatization level and/or cold stimulus intensity. Role of PTH in NST is substantiated by its positive relationships with whole-body metabolic preference for lipids, BAT volume and UCP1 content.
Genetically encoded split luciferase biosensors to measure endosome disruption in real time in live cells
Authors: Kilchrist Kameron V. , Tierney J. William , Duvall Craig L. 
Published: January 2020

AbstractEndosomal escape is a critical step in intracellular delivery of biomacromolecular drugs, but quantitative, high throughput study of endosomal vesicle disruption remains elusive. We designed two genetically encoded split luciferase “turn on” reporters that can be assayed rapidly in well plates on live cells using a luminometer. Both systems use non-luminescent N-terminal and C-terminal luciferase fragments which can reconstitute a functional luminescent enzyme when they are held in proximity by their fusion partners. The first system uses Gal8 and CALCOCO2 fused to these fragments, which interact following endosome disruption and facilitate complementation of the split luciferase fragments to produce significant luminescence when luciferin is added. The second system uses the N-terminal carbohydrate recognition domain of Gal8 (G8-NCRD) fused to both luciferase fragments. Following endosome disruption, G8-NCRD binds to exposed glycans inside endosomes, concentrating both fragments there to reconstitute active luciferase. Additionally, and in contrast to recently reported Gal8 intracellular tracking with fluorescent microscopy, these split luciferase-based assays enable simultaneous identification and downselection of cytotoxic test conditions because the luciferase reaction requires intracellular ATP. Further, we demonstrate that the lead luminescent cell line is more sensitive to detection of endosomal disruption at lower doses of an endosome disrupting drug carrier than the previously reported Gal8-YFP fluorescent system. These systems represent a first-in-class luminescent assay to detect endosome disruption in high throughput while excluding toxic formulations. Endosome disruption screening with these “turn on” systems has potential as a tool in the discovery and development of intracellular biologic drug delivery formulations.Graphical Abstract
Proteome specialization of anaerobic fungi during ruminal degradation of recalcitrant plant fiber
Authors: Hagen Live H. , Brooke Charles G. , Shaw Claire , Norbeck Angela D. , Piao Hailan , Arntzen Magnus Ø. , Brewer Heather , Copeland Alex , Isern Nancy , Shukla Anil , Roux Simon , Lombard Vincent , Henrissat Bernard , O’Malley Michelle A. , Grigoriev Igor V. , Tringe Susannah , Mackie Roderick , Pasa-Tolic Ljiljana , Pope Phillip B. , Hess Matthias 
Published: January 2020

AbstractThe rumen harbors a complex microbial mixture of archaea, bacteria, protozoa and fungi that efficiently breakdown plant biomass and its complex dietary carbohydrates into soluble sugars that can be fermented and subsequently converted into metabolites and nutrients utilized by the host animal. While rumen bacterial populations have been well documented, only a fraction of the rumen eukarya are taxonomically and functionally characterized, despite the recognition that they contribute to the cellulolytic phenotype of the rumen microbiota. To investigate how anaerobic fungi actively engage in digestion of recalcitrant fiber that is resistant to degradation, we resolved genome-centric metaproteome and metatranscriptome datasets generated from switchgrass samples incubated for 48 hours in nylon bags within the rumen of cannulated dairy cows. Across a gene catalogue covering anaerobic rumen bacteria, fungi and viruses, a significant portion of the detected proteins originated from fungal populations. Intriguingly, the carbohydrate-active enzyme (CAZyme) profile suggested a domain-specific functional specialization, with bacterial populations primarily engaged in the degradation of polysaccharides such as hemicellulose, whereas fungi were inferred to target recalcitrant cellulose structures via the detection of a number of endo- and exo-acting enzymes belonging to the glycoside hydrolase (GH) family 5, 6, 8 and 48. Notably, members of the GH48 family were amongst the highest abundant CAZymes and detected representatives from this family also included dockerin domains that are associated with fungal cellulosomes. A eukaryote-selected metatranscriptome further reinforced the contribution of uncultured fungi in the ruminal degradation of recalcitrant fibers. These findings elucidate the intricate networks ofin siturecalcitrant fiber deconstruction, and importantly, suggests that the anaerobic rumen fungi contribute a specific set of CAZymes that complement the enzyme repertoire provided by the specialized plant cell wall degrading rumen bacteria.
Wheelchair user’s voice: a pilot study in Indonesia
Authors: Vasquez Stephanie Gabela , D’Innocenzo Megan E. , Pearlman Jon , Zigler Christy , Mendez Yasmin Garcia , Rozen Perth , Dewi Eviana Hapsari , Praptoraharjo Ignatius 
Published: January 2020

AbstractThere is a significant unmet need for appropriate wheelchairs worldwide. As a whole, studies suggest that appropriate wheelchairs have a positive impact on the quality of life and health of wheelchair users, which is consistent with the goals and outcomes in more resourced settings, and that when services are provided along with the wheelchair, the positive impact is increased. The gaps in previous research, along with the global focus on evidence-based decision making, were strong motivators for carrying out a study that contrasted the outcomes associated with different types of wheelchair service provision strategies. This study used a sample of participants randomly selected from a waitlist (N= 142) or people who used wheelchairs as their primary means of mobility. Two different groups were included, the 8-Steps group and the Standard of Care (SOC)group. The 8-Steps group (N= 118) received wheelchairs from service providers trained using the World Health Organization (WHO) 8-Step process and the SOC group (N=24) received hospital-style wheelchairs and standard care. Interviews were conducted at baseline and a follow up 3-6 months after distribution, to collect data using the following tools: International Society of Wheelchair Professionals (ISWP) Minimum Uniform Data Set (MUD), Wheelchair Skills Test Questionnaire (WST-Q), and Life Satisfaction Questionnaire (LiSAT-11), and Breakdown and Adverse Consequences Questionnaire (BAC-Q).Across-group statistical comparisons were not attempted. The majority of participants from the 8-Steps group used their wheelchair every day for more than 8 hours a day. In contrast, the SOC group used their wheelchairs less than 6 hours a day. Both groups traveled less than 500 meters per day. Participants’ WST-Q scores were low, <65%, at both baseline and endline, with a significant decrease at endline. No significant differences were found when comparing device satisfaction across wheelchairs types. The majority (n=87; 72.7%) of 8-Steps group participants reported performing wheelchair maintenance. Less than half (n=9; 37.5%) of the SOC group reported performing maintenance activities. For both groups, the most reported maintenance activity was wiping or washing the wheelchair, and most wheelchair repairs were performed by the study participant or a family member. The results of this study demonstrate the importance of the WHO 8-steps training package for wheelchair provision. Further studies, training services, and wheelchair skills are needed in low and middle-income countries for both wheelchair users and service providers.
Iterative Refinement of Cellular Identity from Single-Cell Data Using Online Learning
Authors: Gao Chao , Preissl Sebastian , Luo Chongyuan , Castanon Rosa , Sandoval Justin , Rivkin Angeline , Nery Joseph R. , Behrens Margarita M. , Ecker Joseph R. , Ren Bing , Welch Joshua D. 
Published: January 2020

AbstractRecent experimental advances have enabled high-throughput single-cell measurement of gene expression, chromatin accessibility and DNA methylation. We previously used integrative non-negative matrix factorization (iNMF) to jointly learn interpretable low-dimensional representations from multiple single-cell datasets using dataset-specific and shared metagene factors. These factors provide a principled, quantitative definition of cellular identity and how it varies across biological contexts. However, datasets exceeding 1 million cells are now widely available, creating computational barriers to scientific discovery. For instance, it is no longer feasible to analyze large datasets using standard pipelines on a personal computer with limited memory capacity. Moreover, there is a need for an algorithm capable of iteratively refining the definition of cellular identity as efforts to create a comprehensive human cell atlas continually sequence new cells.To address these challenges, we developed an online learning algorithm for integrating large and continually arriving single-cell datasets. We extended previous online learning approaches for NMF to minimize the expected cost of a surrogate function for the iNMF objective. We also derived a novel hierarchical alternating least squares algorithm for iNMF and incorporated it into an efficient online algorithm. Our online approach accesses the training data as mini-batches, decoupling memory usage from dataset size and allowing on-the-fly incorporation of new datasets as they are generated. The online implementation of iNMF converges much more quickly using a fraction of the memory required for the batch implementation, without sacrificing solution quality. Our new approach processes 1.3 million single cells from the entire mouse embryo on a laptop in 25 minutes using less than 500 MB of RAM. We also analyze large datasets without downloading them to disk by streaming them over the internet on demand. Furthermore, we construct a single-cell multi-omic cell atlas of the mouse motor cortex by iteratively incorporating eight single-cell RNA-seq, single-nucleus RNA-seq, single-nucleus ATAC-seq, and single-nucleus DNA methylation datasets generated by the BRAIN Initiative Cell Census Network.Our approach obviates the need to recompute results each time additional cells are sequenced, dramatically increases convergence speed, and allows processing of datasets too large to fit in memory or on disk. Most importantly, it facilitates continual refinement of cell identity as new single-cell datasets from different biological contexts and data modalities are generated.
Growing leaders in schools and out: building internal capacity for the mid-21st-century
Authors: Drago-Severson Eleanor , Blum-DeStefano Jessica 
Published: January 2020

Purpose
This article highlights key elements of a developmental approach to leadership development and their promising connections to mid-21st-century capacities.

Methods
To do so, the authors draw from more than three decades of mixed-methods and qualitative research, as well as insights from their teaching and consulting with leaders of all kinds about adult development.

Findings
Specifically, four critical strategies are highlighted for enhancing collaboration that can help build internal capacity in schools and organizations.

Value
This research shows that building internal capacity in this way can help prepare leaders – and those in their schools and communities – for the complexities and opportunities of mid-21st-century leadership and learning.
In the face of digitalization and AI - Organizations need to take an EPIC approach to learning
Authors: Kimmerle Joachim 
Published: January 2020

Purpose
In this viewpoint article four areas are considered that are relevant for organizational learning.

Design/methodology/approach
These areas are analyzed against the background of digitalization and AI.

Findings
In introducing the EPIC approach, special attention is paid to the relevance of education, the role of patience, the importance of promoting innovation, and the desirability of supporting collaboration.

Originality/value
Our educational system must aim to prepare us for the challenges of organizational learning. We must learn to have the patience to meet these challenges, for only then will we achieve real innovation which we can develop in collaboration with others, in a learning organization that is truly worthy of the name.
Assessment of user's satisfaction with neighbourhood facilities in public housing estates in Akure, Nigeria
Authors: Fakere Alexander Adeyemi , Duke-Henshaw Oluwadunsin Faith 
Published: January 2020

Purpose
This study aims at evaluating the state of neighbourhood facilities and how this influences the well-being of the residents taking into consideration their perception and satisfaction with the facilities. This is because availability and accessibility of neighbourhood facilities in housing estates play important roles in the quality of life of the residents.

Design/methodology/approach
The paper adopts a cross-sectional survey of 301 housing units using structured questionnaire and direct observations in three public housing estates in Akure, namely, Ijapo, Alagbaka and Oba-Ile Housing Estates. Data obtained were analysed using descriptive analysis, mean scoring and categorical regression analysis to examine the effects of adequacy, accessibility and physical condition of the neighbourhood facilities on user’s satisfaction.

Findings
The findings showed that religious centres had the highest rating in all aspects of the study in the study estates, whereas fire service station was rated the least. Most of the independent variables significantly explained satisfaction except for accessibility to schools. The model explained 98.2 per cent of the variance in the level of satisfaction with Multiple R2 of 0.982 and p = 0.000.

Practical implications
The findings imply that there should be proper planning and regular maintenance of neighbourhood facilities within the housing estates in Akure to enhance user’s satisfaction with such facilities.

Originality/value
The study highlights the benefits of having neighbourhood facilities that are adequate, accessible and in good condition to enhance user’s satisfaction.