bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive bioinformatics analysis ofL1CAMgene revealed Novel Pathological mutations associated with L1 syndrome
Authors: Murshed Naseem S. , Mustafa Mujahed I. , Abdelmoneim Abdelrahman H. , Mahmoud Thwayba A. , Elfadol Nafisa M. , Hassan Mohamed A. 
Published: February 2019

AbstractBackgroundMutations in the human L1CAM gene cause a group of neurodevelopmental disorders known as L1 syndrome (CRASH syndrome). The L1CAM gene provides instructions for producing the L1 protein, which is found all over the nervous system on the surface of neurons. L1 syndrome involves a variety of characteristics but the most common characteristic is muscle stiffness. Patients with L1 syndrome can also suffer from difficulty speaking, seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain.MethodThe human L1CAM gene was studied from dbSNP/NCBI, 1499 SNPs were Homo sapiens; of which 450 were missense mutations. This selected for Comprehensive bioinformatics analysis by several in silico tools to investigate the effect of SNPs on L1CAM protein’s structure and function.Results34 missense mutations (26 novel mutations) out of 450 nsSNPs that are found to be the most deleterious that effect on the L1CAM structural and functional level.ConclusionBetter understanding of L1 syndrome caused by mutations in L1CAM gene was achieved using Comprehensive bioinformatics analysis. These findings describe 35 novel L1 mutations which improve our understanding on genotype-phenotype correlation. And can be used as diagnostic markers for L1 syndrome and besides in cancer diagnosis specifically in breast cancer.
Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism
Authors: Fox Nicholas G. , Yu Xiaodi , Feng Xidong , Bailey Henry J. , Martelli Alain , Nabhan Joseph F. , Strain-Damerell Claire , Bulawa Christine , Yue Wyatt W. , Han Seungil 
Published: February 2019

AbstractIron-sulfur clusters (ISC) are essential in all life forms and carry out many crucial cellular functions. The core machinery for de novo ISC biosynthesis, located in the mitochondria matrix, is a five-protein complex containing the cysteine desulfurase NFS1 that is activated by frataxin (FXN), scaffold protein ISCU, accessory protein ISD11, and acyl-carrier protein ACP. Deficiency in FXN leads to the loss-of-function neurodegenerative disorder Friedreich’s ataxia (FRDA). Recently crystal structures depicting the inactive 3- and 4-way sub-complexes of the ISC biosynthesis machinery, lacking the key activator FXN, have been determined. Here, the 3.2 Å resolution cryo-electron microscopy structure of the FXN-bound active human complex, containing two copies of the NFS1-ISD11-ACP-ISCU-FXN hetero-pentamer, delineates for the first time in any organism the interactions of FXN with the component proteins. FXN binds at the interface of two NFS1 and one ISCU subunits, modifying the local environment of a bound zinc ion that would otherwise inhibit NFS1 activity in complexes without FXN. Our structure sheds light on how FXN facilitates ISC production through unlocking the zinc inhibition and stabilizing key loop conformations of NFS1 and ISCU at the protein-protein interfaces, and offers an explanation of how FRDA clinical mutations affect complex formation and FXN activation.
Feeding Kinematics And Morphology Of The Alligator Gar (Atractosteus Spatula, Lacépède, 1803): Feeding Mechanics Of Atractosteus Spatula
Authors: Lemberg Justin B. , Shubin Neil H. , Westneat Mark W. 
Published: February 2019

ABSTRACTModern (lepisosteid) gars are a small clade of seven species and two genera that occupy an important position on the actinopterygian phylogenetic tree as members of the Holostei (Amia+ gars), sister-group of the teleost radiation. Often referred to as “living fossils,” these taxa preserve many plesiomorphic characteristics used to interpret and reconstruct early osteichthyan feeding conditions. Less attention, however, has been paid to the functional implications of gar-specific morphology, thought to be related to an exclusively ram-based, lateral-snapping mode of prey capture. Previous studies of feeding kinematics in gars have focused solely on members of the narrow-snoutedLepisosteusgenus, and here we expand that dataset to include a member of the broad-snouted sister-genus and largest species of gar, the alligator gar (Atractosteus spatula, Lacépède, 1803). High-speed videography reveals that the feeding system of alligator gars is capable of rapid expansion from anterior-to-posterior, precisely timed in a way that appears to counteract the effects of a bow-wave during ram-feeding and generate a unidirectional flow of water through the feeding system. Reconstructed cranial anatomy based on contrast-enhanced micro-CT data show that a lateral-sliding palatoquadrate, flexible intrasuspensorial joint, pivoting interhyal, and retractable pectoral girdle are all responsible for increasing the range of motion and expansive capabilities of the gar cranial linkage system. Muscular reconstructions and manipulation experiments show that, while the sternohyoideus is the primary input to the feeding system (similar to other “basal” actinopterygians), additional input from the hyoid constrictors and hypaxials play an important role in decoupling and modulating between the dual roles of the sternohyoideus: hyoid retraction (jaw opening) and hyoid rotation (pharyngeal expansion) respectively. The data presented here demonstrate an intricate feeding mechanism, capable of precise control with plesiomorphic muscles, that represents one of the many ways the ancestral osteichthyan feeding mechanism has been modified for prey capture.RESEARCH HIGHLIGHTSAlligator gars use a surprisingly expansive cranial linkage system for prey capture that relies on specialized joints for increased mobility and is capable of precise modulation from anterior to posterior using plesiomorphic osteichthyan musculature.
Evaluation of methods to assign cell type labels to cell clusters from single-cell RNAsequencing data
Authors: Díaz-Mejía J. Javier , Meng Elaine C. , Pico Alexander R. , MacParland Sonya A. , Ketela Troy , Pugh Trevor J. , Bader Gary D. , Morris John H. 
Published: February 2019

AbstractIdentification of cell type subpopulations from complex cell mixtures using single-cell RNA-sequencing (scRNA-seq) data includes automated computational steps like data normalization, dimensionality reduction and cell clustering. However, assigning cell type labels to cell clusters is still conducted manually by most researchers, resulting in limited documentation, low reproducibility and uncontrolled vocabularies. Two bottlenecks to automating this task are the scarcity of reference cell type gene expression signatures and that some dedicated methods are available only as web servers with limited cell type gene expression signatures. In this study, we benchmarked four methods (CIBERSORT, GSEA, GSVA, and ORA) for the task of assigning cell type labels to cell clusters from scRNA-seq data. We used scRNA-seq datasets from liver, peripheral blood mononuclear cells and retinal neurons for which reference cell type gene expression signatures were available. Our results show that, in general, all four methods show a high performance in the task as evaluated by Receiver Operating Characteristic curve analysis (average AUC = 0.94, sd = 0.036), whereas Precision-Recall curve analyses show a wide variation depending on the method and dataset (average AUC = 0.53, sd = 0.24). CIBERSORT and GSVA were the top two performers. Additionally, GSVA was the fastest of the four methods and was more robust in cell type gene expression signature subsampling simulations. We provide an extensible framework to evaluate other methods and datasets at https://github.com/jdime/scRNAseq_cell_cluster_labeling.
Amplification-free Library Preparation Improves Quality of Hi-C Analysis
Authors: Niu Longjian , Shen Wei , Huang Yingzhang , He Na , Zhang Yuedong , Sun Jialei , Wan Jing , Jiang Daxin , Yang Manyun , Tse Yu Chung , Li Li , Hou Chunhui 
Published: February 2019

AbstractPCR amplification of Hi-C libraries introduces unusable duplicates and results in a biased representation of chromatin interactions. We present a simplified, fast, and economically efficient Hi-C library preparation procedure that generates sufficient non-amplified ligation products for deep sequencing from 30 million Drosophila cells. Comprehensive analysis of the resulting data indicates that amplification-free Hi-C preserves higher complexity of chromatin interaction and lowers sequencing depth dramatically for the same number of unique paired reads. For human cells which has a large genome, this method recovers an amount of ligated fragments enough for direct high-throughput sequencing without amplification on as low as 250 thousand of cells. Comparison with published in situ Hi-C on millions of human cells reveals that amplification introduces distance-dependent amplification bias, which results in increasing background noise level against genomic distance. With amplification bias avoided, our method may produce a chromatin interaction network more faithfully reflecting the real three-dimensional genomic architecture.
A global survey of mycobacterial diversity in soil
Authors: Walsh Corinne M. , Gebert Matthew J. , Delgado-Baquerizo Manuel , Maestre Fernando T. , Fierer Noah 
Published: February 2019

AbstractMycobacteriumis a diverse bacterial genus ubiquitous in many soil and aquatic environments. Members of this genus have been associated with human and other animal diseases, including the nontuberculous mycobacteria (NTM), which are of growing relevance to public health worldwide. Although soils are often considered an important source of environmentally-acquired NTM infections, the biodiversity and ecological preferences of soil mycobacteria remain largely unexplored across contrasting climates and ecosystem types. Using a culture-independent approach by combining 16S rRNA marker gene sequencing with mycobacterial-specific hsp65 gene sequencing, we analyzed the diversity, distributions, and environmental preferences of soil-dwelling mycobacteria in 143 soil samples collected from across the globe. The surveyed soils harbored highly diverse mycobacterial communities that span the full-extent of the known mycobacterial phylogeny, with most soil mycobacteria belonging to previously undescribed lineages. While the genusMycobacteriumtended to have higher relative abundances in cool, wet, and acidic soil environments, several individual mycobacterial clades had contrasting environmental preferences. We identified the environmental preferences of many mycobacterial clades, including the clinically-relevantM. aviumcomplex that was more commonly detected in wet and acidic soils. However, most of the soil mycobacteria detected were not closely related to known pathogens, calling into question previous assumptions about the general importance of soil as a source of NTM infections. Together this work provides novel insights into the diversity, distributions and ecological preferences of soil mycobacteria, and lays the foundation for future efforts to link mycobacterial phenotypes to their distributions.ImportanceMycobacteria are common inhabitants of soil, and while most members of the bacterial genus are innocuous, some mycobacteria can cause environmentally-acquired infections of humans and other animals. Human infections from nontuberculous mycobacteria (NTM) are increasingly prevalent worldwide, and some areas appear to be ‘hotspots’ for NTM disease. While exposure to soil is frequently implicated as an important mode of NTM transmission, the diversity, distributions and ecological preferences of soil mycobacteria remain poorly understood. We analyzed 143 soils from across the globe and found that the genusMycobacteriumand lineages within the genus often exhibited predictable preferences for specific environmental conditions. Soils harbor large amounts of previously-undescribed mycobacterial diversity, and lineages that include known pathogens were rarely detected in soil. Together these findings suggest that soil is an unlikely source of many mycobacterial infections. The biogeographical patterns we documented lend insight into the ecology of this important group of soil-dwelling bacteria.
RUNX/CBFβ transcription factor complexes promote the phenotypic plasticity of metastatic breast cancer cells
Authors: Ran Ran , Harrison Hannah , Ariffin Nur Syamimi , Ayub Rahna , Pegg Henry J , Deng Wensheng , Mastro Andrea , Ottewell Penny D. , Fowles Anna M. , Blyth Susan M. Mason Karen , Holen Ingunn , Shore Paul 
Published: February 2019

AbstractEpithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show that the plasticity of metastatic breast cancer cells can be promoted by the activity of the RUNX transcription factors. We demonstrate that the RUNX co-regulator CBFβ is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells. We subsequently show, using an inducible CBFβ system, that the MET can be reversed, thus demonstrating the plasticity of RUNX/CBFβ-mediated EMT. Moreover, the MET can be reversed by expression of the EMT transcription factor Slug whose expression is dependent on CBFβ, RUNX1 and RUNX2. Finally, we demonstrate that loss of CBFβ inhibits the ability of metastatic breast cancer cells to invade bone cell cultures and suppresses their ability to form bone metastasesin vivo. Together our findings demonstrate that the RUNX/CBFβ complexes can determine the plasticity of the metastatic cancer cell phenotypes, suggesting that their regulation in different micro-environments may play a key role in the establishment of metastatic tumours.
High-coverage, long-read sequencing of Han Chinese trio reference samples
Authors: Wang Ying-Chih , Olson Nathan D , Deikus Gintaras , Shah Hardik , Wenger Aaron M , Trow Jonathan , Xiao Chunlin , Sherry Stephen , Salit Marc L. , Zook Justin M , Smith Melissa , Sebra Robert 
Published: February 2019

AbstractSingle-molecule long-read sequencing datasets were generated for a son-father-mother trio of Han Chinese descent that is part of the Genome In a Bottle (GIAB) consortium portfolio. The dataset was generated using the Pacific Biosciences Sequel System. The son and each parent were sequenced to an average coverage of 60 and 30, respectively, with N50 subread lengths between 16 and 18 kb. Raw reads and reads aligned to both the GRCh37 and GRCh38 are available at the NCBI GIAB ftp site (ftp://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/data/ChineseTrio/) and the raw read data is archived in NCBI SRA (SRX4739017, SRX4739121, and SRX4739122). This dataset is available for anyone to develop and evaluate long-read bioinformatics methods.
Analysis of novel hyperosmotic shock response suggests “beads in liquid” cytosol structure
Authors: Alexandrov A.I. , Grosfeld E.V. , Dergalev A.A. , Kushnirov V.V. , Chuprov-Netochin R.N. , Tyurin-Kuzmin P.A. , Kireev I.I. , Ter-Avanesyan M.D. , Leonov S.V. , Agaphonov М.O. 
Published: February 2019

AbstractProteins can aggregate in response to stresses, including hyperosmotic shock. Formation and disassembly of aggregates is a relatively slow process. We describe a novel instant response of the cell to hyperosmosis, during which chaperones and other proteins form numerous foci with properties uncharacteristic of classical aggregates. These foci appeared/disappeared seconds after shock onset/removal, in close correlation with cell volume changes. Genome-wide and targeted testing revealed chaperones, metabolic enzymes, P-body components and amyloidogenic proteins in the foci. Most of these proteins can form large assemblies and for some, the assembled state was pre-requisite for participation in foci. A genome-wide screen failed to identify genes whose absence prevented foci participation by Hsp70. Shapes of and interconnections between foci revealed by super-resolution microscopy indicated that the foci were compressed between other entities. Based on our findings, we propose a new model of the cytosol architecture as a collection of numerous of gel-like regions suspended in a liquid network. This network is reduced in volume in response to hyperosmosis and forms small pockets between the gel-like regions.
A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome
Authors: Richardson Tom G , Hemani Gibran , Gaunt Tom R , Relton Caroline L , Smith George Davey 
Published: February 2019

AbstractBackgroundDeveloping insight into tissue-specific transcriptional mechanisms can help improve our understanding of how genetic variants exert their effects on complex traits and disease. By applying the principles of Mendelian randomization, we have undertaken a systematic analysis to evaluate transcriptome-wide associations between gene expression across 48 different tissue types and 395 complex traits.ResultsOverall, we identified 100,025 gene-trait associations based on conventional genome-wide corrections (P < 5 × 10−08) that also provided evidence of genetic colocalization. These results indicated that genetic variants which influence gene expression levels in multiple tissues are more likely to influence multiple complex traits. We identified many examples of tissue-specific effects, such as genetically-predicted TPO, NR3C2 and SPATA13 expression only associating with thyroid disease in thyroid tissue. Additionally, FBN2 expression was associated with both cardiovascular and lung function traits, but only when analysed in heart and lung tissue respectively.We also demonstrate that conducting phenome-wide evaluations of our results can help flag adverse on-target side effects for therapeutic intervention, as well as propose drug repositioning opportunities. Moreover, we find that exploring the tissue-dependency of associations identified by genome-wide association studies (GWAS) can help elucidate the causal genes and tissues responsible for effects, as well as uncover putative novel associations.ConclusionsThe atlas of tissue-dependent associations we have constructed should prove extremely valuable to future studies investigating the genetic determinants of complex disease. The follow-up analyses we have performed in this study are merely a guide for future research. Conducting similar evaluations can be undertaken systematically at http://mrcieu.mrsoftware.org/Tissue_MR_atlas/.
Transcriptional variation in glucosinolate biosynthetic genes and inducible responses to aphid herbivory on field-grownArabidopsis thaliana
Authors: Sato Yasuhiro , Tezuka Ayumi , Kashima Makoto , Deguchi Ayumi , Shimizu-Inatsugi Rie , Yamazaki Misako , Shimizu Kentaro K. , Nagano Atsushi J. 
Published: February 2019

AbstractRecently, increasing attempts have been made to understand how plant genes functionin naturastudies. To determine whether plant defense genes are activated under multiple biotic stimuli, we combined a high-throughput RNA-Seq with insect survey data on 19 accessions ofArabidopsis thalianagrowing on the field site of Switzerland. We found that genes with GO annotations “glucosinolate biosynthetic process” and “response to insects” were the most significantly enriched, exhibiting largely variable expression among plant accessions. Nearly half of the total expression variation in glucosinolate biosynthetic genes,AOPs, ESM1, ESP,andTGG1,was explained by among-accession variance. Combined with the field RNA-Seq data, bioassays confirmed thatAOP3was up-regulated in response to the mustard aphidLipaphis erysimi.In addition, we also found that the expression of a major cis-jasmone activated geneCYP81D11was positively correlated with the number of the flea beetlesPhyllotretaspp. The combined results from RNA-Seq and insect surveys suggested that plants can activate their defenses even when they are exposed to multiple biotic stimuliin natura.
The expanded halo model of brand image, country image and product image in the context of three Asian countries
Authors: Woo Hongjoo 
Published: February 2019

Purpose
The purpose of this paper is to examine an alternate halo model across the context of South Korea, China and India, and provide expanded interrelationships among their major brands’ brand images, country images, general product images and category-specific images (electronics and fashion handbags).

Design/methodology/approach
The proposed hypotheses in the alternate halo model were tested through a quantitative (survey) approach.

Findings
The results of analyzing 305 American consumers’ responses suggest theoretical and marketing implications for Asian countries in utilizing brand image effect and cross-category halo effects in marketing products in the global market.

Originality/value
The study proposes an alternate country image model that can be applied to the context of Asian countries with relatively immature country image, which is expanded from the traditional models in literature.
Athletes’ brand equity, spectator satisfaction, and behavioral intentions
Authors: Park Jae-Ahm , Sung Jun-Mo , Son Jae-Man , Na Kyunga , Kim Suk-Kyu 
Published: February 2019

Purpose
The purpose of this paper is to examine the relationships among an individual athlete’s brand equity, overall spectator satisfaction at sporting events and behavioral intentions.

Design/methodology/approach
The convenience sampling method was used when approaching potential participants among spectators of the LG Whisen Rhythmic All Stars 2013, a sporting event in which celebrated sports players perform choreographed dance routines. A total of 350 surveys were completed in Go-Yang, South Korea. Of the surveys collected, 20 were discarded due to excessive missing values, resulting in 330 usable surveys.

Findings
Using structural equation modeling, this study found that the brand equity of an individual athlete positively and directly affects the overall sporting event satisfaction and behavioral intentions, including re-purchase and word-of-mouth intentions among event attendees, which are factors that are mediated indirectly by satisfaction.

Originality/value
This study shows that the brand equity of an individual athlete can increase the spectator satisfaction levels in a similar manner to the brand equity of a sports team or product.