bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids
Authors: Turner Natalie , Mikalauskaite Deimante , Barone Krista , Flaherty Kathleen , Senevirathne Gayani , Adachi Noritaka , Shubin Neil H , Nakamura Tetsuya 
Published: May 2019

AbstractAppendage patterning and evolution have been active areas of inquiry for the past two centuries. While most work has centered on the skeleton, particularly that of amniotes, the evolutionary origins and molecular underpinnings of the neuromuscular diversity of fish appendages have remained enigmatic. The fundamental pattern of segmentation in amniotes, for example, is that all muscle precursors and spinal nerves enter either the paired appendages or body wall at the same spinal level. The condition in finned vertebrates is not understood. To address this gap in knowledge, we investigated the development of muscles and nerves in unpaired and paired fins of skates and compared them to those of chain catsharks. During skate and shark embryogenesis, cell populations of muscle precursors and associated spinal nerves at the same axial level contribute to both appendages and body wall, perhaps representing an ancestral condition of gnathostome appendicular neuromuscular systems. Remarkably in skates, this neuromuscular bifurcation as well as colinearHoxexpression extend posteriorly to pattern a broad paired fin domain. In addition, we identified migratory muscle precursors (MMPs), which are known to develop into paired appendage muscles withPax3andLbx1gene expression, in the dorsal fins of skates. Our results suggest that muscles of paired fins have evolved via redeployment of the genetic program of MMPs that were already involved in dorsal fin development. Appendicular neuromuscular systems most likely have emerged as side branches of body wall neuromusculature and have been modified to adapt to distinct aquatic and terrestrial habitats.
Histone acetylome-wide association study of tuberculosis
Authors: del Rosario Ricardo C.H. , Poschmann Jeremie , Kumar Pavanish , Cheng Catherine Y. , Ong Seow Theng , Hajan Hajira Shreen , Kumar Dilip , Marzuki Mardiana , Lu Xiaohua , Lee Andrea , Tang Yanxia , Chee Cynthia Bin Eng , Lim Carey , Lee Bernett , Lum Josephine , Zolezzi Francesca , Poidinger Michael , Rotzschke Olaf , Khor Chiea Chuen , Wang Yee T. , Chandy K. George , De Libero Gennaro , Singhal Amit , Prabhakar Shyam 
Published: May 2019

AbstractHost-cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Chinese discovery cohort, which were validated in a subsequent multi-ethnic cohort, thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression in a third cohort. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulated Akt-mTOR signaling and promoted Mtb clearance in vitro. We performed histone acetylation QTL analysis on the dataset and identified candidate causal variants for immune phenotypes. Our study serves as proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.
Exploring Contextual Interference in Implicit and Explicit Motor Learning
Authors: Dang Kristy V. , Parvin Darius E. , Ivry Richard B. 
Published: May 2019

AbstractThe classic advice given to anyone learning a new skill is “practice makes perfect.” While this provides a good general rule to follow, it lacks any detail on what form of practice will efficiently maximize learning. So when faced with the task of acquiring multiple skills, what is the optimal way to learn? Would it be more beneficial to master each skill separately or learn them all at once in an interleaved fashion? A concept known as contextual interference suggests that using a random practice schedule leads to better retention than a blocked one. There are some motor learning studies that are consistent with this hypothesis and some that are not. In order to explore these conflicting results, we applied contextual interference to a simple reaching task that could allow us to observe its effects to various components of motor learning. We had participants learn three different visuomotor rotations and manipulated interference by placing them in groups characterized by how training targets are ordered (blocked vs. random). Using reaction time and hand angle as our measures of performance, we found that participants who experienced a random practice schedule had significant improvements in their ability to retain information, which was manifest as higher levels of implicit adaptation and faster reaction times. However, this did not necessarily mean the information was executed accurately since hand angles did not differ between groups. These findings suggest contextual interference will be most advantageous in situations that require fast explicit recall of a motor plan to use rather than those that emphasize accuracy.
Inferring diploid 3D chromatin structures from Hi-C data
Authors: Cauer Alexandra Gesine , Yardimci Gürkan , Vert Jean-Philippe , Varoquaux Nelle , Noble William Stafford 
Published: May 2019

AbstractThe 3D organization of the genome plays a key role in many cellular processes, such as gene regulation, differentiation, and replication. Assays like Hi-C measure DNA-DNA contacts in a high-throughput fashion, and inferring accurate 3D models of chromosomes can yield insights hidden in the raw data. For example, structural inference can account for noise in the data, disambiguate the distinct structures of homologous chromosomes, orient genomic regions relative to nuclear landmarks, and serve as a framework for integrating other data types. Although many methods exist to infer the 3D structure of haploid genomes, inferring a diploid structure from Hi-C data is still an open problem. Indeed, the diploid case is very challenging, because Hi-C data typically does not distinguish between homologous chromosomes. We propose a method to infer 3D diploid genomes from Hi-C data. We demonstrate the accuarcy of the method on simulated data, and we also use the method to infer 3D structures for mouse chromosome X, confirming that the active homolog exhibits a bipartite structure, whereas the active homolog does not.
Nested Active Learning for Efficient Model Contextualization and Parameterization: Pathway to generating simulated populations using multi-scale computational models
Authors: Cockrell Chase , Ozik Jonathan , Collier Nick , An Gary 
Published: May 2019

AbstractThere is increasing interest in the use of mechanism-based multi-scale computational models (such as agent-based models) to generate simulated clinical populations in order to discover and evaluate potential diagnostic and therapeutic modalities. The description of the environment in which a biomedical simulation operates (model context) and parameterization of internal model rules (model content) requires the optimization of a large number of free-parameters. In this work, we utilize a nested active-learning workflow to efficiently parameterize and contextualize an agent-based model (ABM) of systemic inflammation used to examine sepsis.MethodsContextual parameter space was examined using four parameters external to the model’s rule-set. The model’s internal parameterization, which represents gene expression and associated cellular behaviors, was explored through the augmentation or inhibition of signaling pathways for 12 signaling mediators associated with inflammation and wound healing. We have implemented a nested active learning approach in which the clinically relevant model environment space for a given internal model parameterization is mapped using a small Artificial Neural Network (ANN). The outer AL level workflow is a larger ANN which uses active learning to efficiently regress the volume and centroid location of the CR space given by a single internal parameterization.ResultsWe have reduced the number of simulations required to efficiently map the clinically relevant parameter space of this model by approximately 99%. Additionally, we have shown that more complex models with a larger number of variables may expect further improvements in efficiency.
Automatic annotation of Cryo-EM maps with the convolutional neural network Haruspex
Authors: Mostosi Philipp , Schindelin Hermann , Kollmannsberger Philip , Thorn Andrea 
Published: May 2019

AbstractIn recent years, three-dimensional density maps reconstructed from single particle images obtained by electron cryo-microscopy (Cryo-EM) have reached unprecedented resolution. However, map interpretation can be challenging, in particular if the constituting structures require de-novo model building or are very mobile. Here, we demonstrate the potential of convolutional neural networks for the annotation of Cryo-EM maps: our network Haruspex has been trained on a carefully curated set of 293 experimentally derived reconstruction maps to automatically annotate protein secondary structure elements as well as RNA/DNA. It can be straightforwardly applied to annotate newly reconstructed maps to support domain placement or to supply a starting point for main-chain placement. Due to its high recall and precision rates of 95.1% and 80.3%, respectively, on an independent test set of 122 maps, it can also be used for validation during model building. The trained network will be available as part of the CCP-EM suite.
The structural unit of melanin in the cell wall of the fungal pathogenCryptococcus neoformans
Authors: Camacho Emma , Vij Raghav , Chrissian Christine , Prados-Rosales Rafael , Gil David , O’Meally Robert N. , Cordero Radames J.B. , Cole Robert N. , McCaffery J. Michael , Stark Ruth E. , Casadevall Arturo 
Published: May 2019

ABSTRACTMelanins are synthesized macromolecules that are found in all biological kingdoms. These pigments have a myriad of roles that range from microbial virulence to key components of the innate immune response in invertebrates. Melanins also exhibit unique properties with potential applications in physics and material sciences, ranging from electrical batteries to novel therapeutics. In the fungi, melanins such as eumelanins, are components of the cell wall that provide protection against biotic and abiotic elements. Elucidation of the smallest fungal cell wall-asociated melanin unit that serves as a building block is critical to understand the architecture of these polymers, its interaction with surrounding components, and their functional versatility. In this study, we used isopycnic gradient sedimentation, NMR, EPR, high-resolution microscopy, and proteomics to analyze the melanin in the cell wall of the human pathogenic fungusCryptococcus neoformans. We observed that melanin is assembled into the cryptococcal cell wall in spherical structures of ∼200 nm in diameter, termed melanin granules, which are in turn composed of nanospheres of ∼30 nm in diameter, the fungal melanosomes. We noted that melanin granules are closely associated with proteins that may play critical roles in the fungal melanogenesis and the supramolecular structure of this polymer. Using this structural information, we propose a model forC. neoformansmelanization that is similar to the process used in animal melanization and is consistent with the phylogenetic relatedness of the fungal and animal kingdoms.
Calcium Sensing Receptor Common Variants Influence the Effects of Serum Calcium on Coronary Artery Disease Risks
Authors: Smelser Diane T. , Hannan Fadil M. , Metpally Raghu P.R. , Krishnamurthy Sarathbabu , Carey David J. , Thakker Rajesh V. , Breitwieser Gerda E. ,   on behalf of the Regeneron Genetics Center
Published: May 2019

AbstractRationaleThe calcium-sensing receptor (CaSR) regulates serum calcium concentrations and common single nucleotide polymorphisms (SNPs) in a carboxyl terminal tri-locus haplotype block contribute to serum calcium variance in the general population. Altered serum calcium concentrations are associated with coronary artery disease (CAD), but direct role for CaSR in CAD remains to be determined.MethodsWe evaluated the associations of serum calcium and common CASR SNPs or the tri-locus haplotype block with major diseases including CAD in 51,289 patients from the DiscovEHR cohort derived from a single US health care system.ResultsSerum calcium concentrations were positively associated with the risk of CAD, and this risk was modified by common CASR SNPs. The Ala986Ser SNP was positively associated with hypercalcemia. Carriers of Ala986Ser had a significantly increased CAD risk whereas Arg990Gly carriers had a reduced risk relative to the reference SNP, for those with albumin-corrected serum calcium from 8.5-9.5 mg/dL. In the context of the tri-locus haplotype, the reduced CAD risk conferred by Arg990Gly remained significant. Analysis of the association of common CASR SNPs with CAD risk factors showed Arg990Gly was negatively associated with the CAD risk factor of chronic kidney disease, but independent of alterations in lipids, hemoglobin A1c, or blood pressure.ConclusionsThis study compares the common approach of single SNP analysis with the impact of a common variant haplotype block and refocuses attention on the CaSR Arg990Gly SNP which reduces the risk of CAD over a specific range of median albumin-corrected calcium concentrations.PrécisClinical data and whole exome sequences from a cohort of 51,289 individuals (DiscovEHR) were used to assess the independent contributions of serum Ca2+ and CASR common variants to cardiovascular diseases including CAD.
Next-generation sequencing of double stranded RNA is greatly improved by treatment with the inexpensive denaturing reagent DMSO
Authors: Wilcox Alexander H. , Delwart Eric , Díaz Muñoz Samuel L. 
Published: May 2019

AbstractDouble stranded RNA (dsRNA) is the genetic material of important viruses and a key component of RNA interference-based immunity in eukaryotes. Previous studies have noted difficulties in determining the sequence of dsRNA molecules that have affected studies of immune function and estimates of viral diversity in nature. Dimethyl sulfoxide (DMSO) has been used to denature dsRNA prior to the reverse transcription stage to improve RT-PCR and Sanger sequencing. We systematically tested the utility of DMSO to improve sequencing yield of a dsRNA virus (Φ6) in a short-read next generation sequencing platform. DMSO treatment improved sequencing read recovery by over two orders of magnitude, even when RNA and cDNA concentrations were below the limit of detection. We also tested the effects of DMSO on a mock eukaryotic viral community and found that dsRNA virus reads increased with DMSO treatment. Furthermore, we provide evidence that DMSO treatment does not adversely affect recovery of reads from a single-stranded RNA viral genome (Influenza A/California/07/2009). We suggest that up to 50% DMSO treatment be used prior to cDNA synthesis when samples of interest are composed of or may contain dsRNA.Data SummarySequence data was deposited in the NCBI Short Read Archive (accession numbers: PRJNA527100, PRJNA527101, PRJNA527098). Data and code for analysis is available on GitHub (https://github.com/awilcox83/dsRNA-sequencing/, doi:10.5281/zenodo.1453423). Protocol for dsRNA sequencing is posted on protocols.io (doi:10.17504/protocols.io.ugnetve).
Enrichment in conservative amino acid changes among fixed and standing missense variations in slow evolving proteins
Authors: Wang Mingrui , Wang Dapeng , Yu Jun , Huang Shi 
Published: May 2019

AbstractProteins were first used in the early 1960s to discover the molecular clock dating method and remain in common usage today in phylogenetic inferences based on neutral variations. To avoid substitution saturation, it is necessary to use slow evolving genes. However, it remains unclear whether fixed and standing missense changes in such genes may qualify as neutral. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Macaca monkey, we found that the fraction of conservative amino acid mismatches between species was significantly higher in slow evolving proteins. We also examined the single nucleotide polymorphisms (SNPs) by using the 1000 genomes project data and found that missense SNPs in slow evolving proteins also had higher fraction of conservative changes, especially for common SNPs, consistent with more natural selection for SNPs, particularly rare ones, in fast evolving proteins. These results suggest that fixed and standing missense variations in slow evolving proteins are more likely to be neutral and hence better qualified for use in phylogenetic inferences.
Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
Authors: Chng Kern Rei , Li Chenhao , Bertrand Denis , Qi Ng Amanda Hui , Kwah Junmei Samantha , Low Hwee Meng , Tong Chengxuan , Natrajan Maanasa , Zhang Michael Hongjie , Xu Licheng , Ki Ko Karrie Kwan , Pei Ho Eliza Xin , Av-Shalom Tamar V. , Pei Teo Jeanette Woon , Khor Chiea Chuen ,   MetaSUB Consortium, Chen Swaine L. , Mason Christopher E. , Oon Tek N , Marimuthu Kalisvar , Ang Brenda , Nagarajan Niranjan 
Published: May 2019

AbstractThere is growing attention surrounding hospital acquired infections (HAIs) due to high associated healthcare costs, compounded by the scourge of widespread multi-antibiotic resistance. Although hospital environment disinfection is well acknowledged to be key for infection control, an understanding of colonization patterns and resistome profiles of environment-dwelling microbes is currently lacking. We report the first extensive genomic characterization of microbiomes (428), common HAI-associated microbes (891) and transmissible drug resistance cassettes (1435) in a tertiary hospital environment based on a 3-timepoint sampling (1 week and >1 year apart) of 179 sites from 45 beds. Deep shotgun metagenomic sequencing unveiled two distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human microbiome influenced environments that display corresponding patterns of divergence over space and time. To study common nosocomial pathogens that were typically present at low abundances, a combination of culture enrichment and long-read nanopore sequencing was used to obtain thousands of high contiguity genomes (2347), phage sequences (1693) and closed plasmids (5910), a significant fraction of which (>60%) are not represented in current sequence databases. These high-quality assemblies and metadata enabled a rich characterization of resistance gene combinations, phage diversity, plasmid architectures, and the dynamic nature of hospital environment resistomes and their reservoirs. Phylogenetic analysis identified multidrug resistant strains as being more widely distributed and stably colonizing across hospital sites. Further genomic comparisons with clinical isolates across multiple species supports the hypothesis that multidrug resistant strains can persist in the hospital environment for extended periods (>8 years) to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in the hospital environment and establishes the feasibility of systematic genomic surveys to help target resources more efficiently for preventing HAIs.
Using virtual reality and thermal imagery to improve statistical modelling of vulnerable and protected species
Authors: Leigh Catherine , Heron Grace , Wilson Ella , Gregory Taylor , Clifford Samuel , Holloway Jacinta , McBain Miles , Gonzalez Felipé , McGree James , Brown Ross , Mengersen Kerrie , Peterson Erin E. 
Published: May 2019

AbstractBiodiversity loss and sparse observational data mean that critical conservation decisions may be based on little to no information. Emerging technologies, such as airborne thermal imaging and virtual reality, may facilitate species monitoring and improve predictions of species distribution. Here we combined these two technologies to predict the distribution of koalas, specialized arboreal foliovores facing population declines in many parts of eastern Australia. For a study area in southeast Australia, we complemented ground-survey records with presence and absence observations from thermal-imagery obtained using Remotely-Piloted Aircraft Systems. These field observations were further complemented with information elicited from koala experts, who were immersed in 360-degree images of the study area. The experts were asked to state the probability of observing a koala at sites they viewed and to assign each probability a confidence rating. We fit logistic regression models to the ground survey data and the ground plus thermal-imagery survey data and a beta regression model to the expert elicitation data. We then combined parameter estimates from the expert-elicitation model with those from each of the survey models to predict koala presence and absence in the study area. The model that combined the ground, thermal-imagery and expert-elicitation data substantially reduced the uncertainty around parameter estimates and increased the accuracy of classifications (koala presence vs absence), relative to the model based on ground-survey data alone. Our findings suggest that data elicited from experts using virtual reality technology can be combined with data from other emerging technologies, such as airborne thermal-imagery, using traditional statistical models, to increase the information available for species distribution modelling and the conservation of vulnerable and protected species.
Shareholder rights, telecommunications and director attendance around the world
Authors: Nowland John 
Published: May 2019

Purpose
This study aims to document the variation in director attendance rates around the world and investigate the influence of cross-country differences in law and infrastructure on director attendance practices.

Design/methodology/approach
Director attendance data are hand-collected from company annual reports and are related to differences in shareholder rights, director liability and transportation and telecommunications infrastructure across countries.

Findings
Using a hand-collected data set of 4,344 directorships from 33 countries, the results indicate that director attendance is significantly lower in emerging markets and is positively related to the extent of shareholder rights and the quality of telecommunications infrastructure.

Originality/value
For policymakers and shareholders, the findings of this study indicate that there is substantial variation in director attendance practices around the world. Across all markets, director attendance is higher when the telecommunications infrastructure better enables the potential for virtual attendance, thereby allowing directors to participate in meetings when they cannot be physically present. In emerging markets, director attendance is also higher where there is a stronger emphasis on shareholder rights, highlighting an avenue for improved director attendance by strengthening shareholder involvement in major corporate decisions.