bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis of progenitor cell dynamics and lineage specification of the human fetal kidney
Authors: Menon Rajasree , Otto Edgar A. , Kokoruda Austin , Zhou Jian , Zhang Zidong , Yoon Euisik , Chen Yu-Chih , Troyanscaya Olga , Spence Jason R. , Kretzler Matthias , Cebrián Cristina 
Published: February 2018

ABSTRACTThe mammalian kidney develops through repetitive and reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons, respectively. Most of our knowledge of the developmental regulators driving this process has been gained from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used singlecell transcriptomics to characterize gene expression in different cell population, and to study individual cell dynamics and lineage trajectories during development. Single cell transcriptome analyses of 3,865 cells identified 17 clusters of specific cell types as defined by their gene expression profile, including markers of ureteric bud tip- and metanephric mesenchyme-specific progenitors, as well as their intermediate and differentiated lineages including the mature collecting ducts, the renal vesicle and comma- and s-shaped bodies, immature and mature podocytes, proximal tubules, loops of Henle and distal tubules. Other lineages identified include mesangium and cortical and medullary interstitium, endothelial and immune cells as well as hematopoietic cells. Novel markers for these cell types were revealed in the analysis as well as components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression array of the human developing kidney at the single-cell level.
Modeling Polypharmacy Side Effects with Graph Convolutional Networks
Authors: Zitnik Marinka , Agrawal Monica , Leskovec Jure 
Published: February 2018

AbstractMotivation: The use of drug combinations, termed polypharmacy, is common to treat patients with complex diseases or co-existing conditions. However, a major consequence of polypharmacy is a much higher risk of adverse side effects for the patient. Polypharmacy side effects emerge because of drug-drug interactions, in which activity of one drug may change, favorably or unfavorably, if taken with another drug. The knowledge of drug interactions is often limited because these complex relationships are rare, and are usually not observed in relatively small clinical testing. Discovering polypharmacy side effects thus remains an important challenge with significant implications for patient mortality and morbidity.Results: Here, we present Decagon, an approach for modeling polypharmacy side effects. The approach constructs a multimodal graph of protein-protein interactions, drug-protein target interactions, and the polypharmacy side effects, which are represented as drug-drug interactions, where each side effect is an edge of a different type. Decagon is developed specifically to handle such multimodal graphs with a large number of edge types. Our approach develops a new graph convolutional neural network for multirelational link prediction in multimodal networks. Unlike approaches limited to predicting simple drug-drug interaction values, Decagon can predict the exact side effect, if any, through which a given drug combination manifests clinically. Decagon accurately predicts polypharmacy side effects, outperforming baselines by up to 69%. We find that it automatically learns representations of side effects indicative of co-occurrence of polypharmacy in patients. Furthermore, Decagon models particularly well polypharmacy side effects that have a strong molecular basis, while on predominantly non-molecular side effects, it achieves good performance because of effective sharing of model parameters across edge types. Decagon opens up opportunities to use large pharmacogenomic and patient population data to flag and prioritize polypharmacy side effects for follow-up analysis via formal pharmacological studies.Availability: Source code and preprocessed datasets are at: http://snap.stanford.edu/decagon.Contact:jure@cs.stanford.edu
Gallic Acid Disrupts Aβ1-42 Aggregation and Rescues Cognitive Decline of APP/PS1 Transgenic Mouse
Authors: Yu Mei , Chen Xuwei , Liu Jihong , Ma Quan , Chen Hao , Zhou Lin , Yang Sen , Zheng Lifeng , Ning Chengqing , Xu Jing , Gao Tianming , Hou Sheng Tao 
Published: February 2018

AbstractAlzheimer’s disease (AD) treatment represents one of the largest unmet medical needs. Developing drugs capable of preventing Aβ aggregation is an excellent approach to prevent and treat AD. Here, we show that gallic acid (GA), a naturally occurring polyphenolic small molecule rich in grape seeds and fruits, has the capacity to alleviate cognitive decline of APP/PS1 transgenic mouse through reduction of Aβ1-42 aggregation and neurotoxicity. Oral administration of GA not only improved the spatial reference memory and spatial working memory of early stage AD mice (4-month-old), but also significantly reduced the more severe deficits in spatial learning, reference memory, short-term recognition and spatial working memory of the late stage AD mice (9-month-old). The hippocampal long-term-potentiation (LTP) was also significantly elevated in the GA-treated late stage APP/PS1 AD mice. Atomic force microscopy (AFM), dynamic light scattering (DLS) and thioflavin T (ThT) fluorescence densitometry analyses showed that GA can reduce Aβ1-42 aggregation from forming toxic oligomers and fibrils. Indeed, pre-incubating GA with oligomeric Aβ1-42 reduced Aβ 1-42-mediated intracellular calcium influx and neurotoxicity. Molecular docking studies identified that the 3,4,5-hydroxyle groups of GA were essential in noncovalently stabilizing GA binding to the Lys28-Ala42 salt bridge and the -COOH group is critical for disrupting the salt bridge of Aβ1-42. The predicated covalent interaction through Schiff-base formation between the carbonyl group of the oxidized product and ε-amino group of Lys16 is also critical for the disruption of Aβ1-42 S-shaped triple-β-motif and toxicity. Together, these studies demonstrated that GA can prevent and protect the AD brain through disrupting Aβ1-42 aggregation.
Super-multiplexed fluorescence microscopy via photostability contrast
Authors: Orth Antony , Ghosh Richik N. , Wilson Emma , Doughney Timothy , Brown Hannah , Reineck Philipp , Thompson Jeremy , Gibson Brant C. 
Published: February 2018

AbstractMany areas of biological research rely heavily on fluorescence microscopy to observe and quantify the inner workings of the cell. Traditionally, multiple types of cellular structures or biomolecules are visualized simultaneously with spectrally distinct fluorescent labels. A high degree of multiplexing is desirable as it affords the experiment greater information content, speeding up research timelines. Multiplexing can be increased by imaging a larger number of spectral channels, however, the wide emission spectra of most fluorophores limits multiplexing to four or five labels in standard fluorescence microscopes. Further multiplexing requires another dimension of contrast. Here, we show that photostability differences can be used to distinguish between fluorescent labels. By combining photobleaching characteristics with a novel unmixing algorithm, we resolve up to three fluorescent labels in a single spectral channel and unmix fluorescent labels with nearly identical emission spectra. We apply our technique to organic dyes, autofluorescent biomolecules and fluorescent proteins, and show that the latter are particularly well suited to our method as their bleaching is often reversible. Our approach has the potential to triple the multiplexing capabilities of any digital widefield or confocal fluorescence microscope with no additional hardware, making it readily accessible to a wide range of researchers.
Two parallel pathways implement robust propionate catabolism and detoxification in mycobacteria
Authors: Tummler Katja , Zimmermann Michael , Schubert Olga T. , Aebersold Ruedi , Kühn Clemens , Sauer Uwe , Klipp Edda 
Published: February 2018

AbstractTuberculosis remains a major global health threat with over 1.5 million deaths each year. Mycobacterium tuberculosis’ success story is related to a flexible metabolism, allowing growth despite restrictive conditions within the human host.Host lipids stores are a major carbon source in vivo. Their catabolism yields propionyl-CoA, which is processed by two parallel pathways, the methylmalonyl CoA pathway and the methylcitrate pathway. Both pathways are considered potential drug targets. The methylcitrate pathway is upregulated in the pathological context. However, intermediates of this pathway can be cytotoxic and Mtb’s preference for its usage remains unclear.We combine thermodynamic kinetic modeling, quantitative proteomics and time-resolved metabolomics to characterize the interplay between the two pathways and to show their functionalities in an efficient and fast propionate catabolism.We find that the methylcitrate pathway acts as a transcriptionally regulated, high capacity catabolic pathway due to its favorable thermodynamics and metabolic control distribution. In contrast, the methylmalonyl pathway is constitutively fulfilling biosynthetic tasks and can quickly detoxify propionate pulses, but is thermodynamically restricted to lower capacity.
Zebrafish sp7 mutants show tooth cycling independent of attachment, eruption and poor differentiation of teeth
Authors: Kague E , Witten P.E , Soenens M , Campos CL , Lubiana T , Fisher S , Hammond C , Robson Brown K , Passos-Bueno MR , Huysseune A 
Published: February 2018

SummaryThe capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted. Without bone of attachment we observed abnormal orientation of teeth, and abnormal connection of pulp cavities of predecessor and replacement teeth. Mutants lacking sp7 show arrested dentinogenesis, with non-polarization of odontoblasts and only a thin layer of dentin deposited. Osteoclast activity was observed in sp7 mutants; due to the lack of bone of attachment, remodelling was diminished but nevertheless present along the pharyngeal bone. We conclude that tooth replacement is ongoing in the sp7 mutant despite poor differentiation and defective attachment. Without bone of attachment tooth orientation and pulp organization are compromised.
Human mediated dispersal of cats in the Neolithic Central Europe
Authors: Baca Mateusz , Popović Danijela , Panagiotopoulou Hanna , Marciszak Adrian , Krajcarz Magdalena , Krajcarz Maciej T. , Makowiecki Daniel , Węgleński Piotr , Nadachowski Adam 
Published: February 2018

AbstractArchaeological and genetic evidence suggest that all domestic cats derive from the Near Eastern wildcat (Felis silvestris lybica) and were domesticated twice, first in the Near East around 10 000 years ago and for the second time in Ancient Egypt ca. 3 500 years ago. The spread of the domesticated form in Europe occurred much later, primarily mediated by Greek and Phoenician traders and afterwards by Romans who introduced cats to Western and Central Europe around 2 000 years ago. We investigated mtDNA of HoloceneFelisremains and provide evidence of an unexpectedly early presence of cats bearing the Near Eastern wildcat mtDNA haplotypes in Central Europe, being ahead of Roman Period by over 2 000 years. The appearance of the Near Eastern wildcats in Central Europe coincide with the peak of Neolithic settlement density, moreover most of those cats belonged to the same mtDNA lineages as those domesticated in the Near East. Thus, although we cannot fully exclude that the Near Eastern wildcats appeared in Central Europe as a result of introgression with European wildcat, our findings strongly support the hypothesis that the Near Eastern wildcats spread across Europe together with the first farmers, perhaps as commensal animals. We also found that cats dated to the Neolithic period belonged to different mtDNA lineages than those brought to Central Europe in Roman times, this supports the hypothesis that the gene pool of contemporary European domestic cats might have been established from two different source populations that contributed in different periods.
Rapid multi-locus sequence typing direct from uncorrected long reads using Krocus
Authors: Page Andrew J. , Keane Jacqueline A. 
Published: February 2018

AbstractGenome sequencing is rapidly being adopted in reference labs and hospitals for bacterial outbreak investigation and diagnostics where time is critical. Seven gene multi-locus sequence typing is a standard tool for broadly classifying samples into sequence types, allowing, in many cases, to rule a sample in or out of an outbreak, or allowing for general characteristics about a bacterial strain to be inferred. Long read sequencing technologies, such as from PacBio or Oxford Nanopore, can produce read data within minutes of an experiment starting, unlike short read sequencing technologies which require many hours/days. However, the error rates of raw uncorrected long read data are very high. We present Krocus which can predict a sequence type directly from uncorrected long reads, and which was designed to consume read data as it is produced, providing results in minutes. It is the only tool which can do this from uncorrected long reads. We tested Krocus on over 600 samples sequenced with using long read sequencing technologies from PacBio and Oxford Nanopore. It provides sequence types on average within 90 seconds, with a sensitivity of 94% and specificity of 97%, directly from uncorrected raw sequence reads. The software is written in Python and is available under the open source license GNU GPL version 3.
The Trials and Tribulations of Priors and Posteriors in Bayesian Timing of Divergence Analyses: the Age of Butterflies Revisited
Authors: Chazot Nicolas , Wahlberg Niklas , Victor Lucci Freitas André , Mitter Charles , Labandeira Conrad , Sohn Jae-Cheon , Sahoo Ranjit Kumar , Seraphim Noemy , De Jong Rienk , Heikkilä Maria 
Published: February 2018

AbstractThe need for robust estimates of times of divergence is essential for downstream analyses, yet assessing this robustness is still rare. We generated a time-calibrated genus-level phylogeny of butterflies (Papilionoidea), including 994 taxa, up to 10 gene fragments and an unprecedented set of 12 fossils and 10 host-plant node calibration points. We compared marginal priors and posterior distributions to assess the relative importance of the former on the latter. This approach revealed a strong influence of the set of priors on the root age but for most calibrated nodes posterior distributions shifted from the marginal prior, indicating significant information in the molecular dataset. We also tested the effects of changing assumptions for fossil calibration priors and the tree prior. Using a very conservative approach we estimated an origin of butterflies at 107.6 Ma, approximately equivalent to the Early Cretaceous–Late Cretaceous boundary, with a credibility interval ranging from 89.5 Ma (mid Late Cretaceous) to 129.5 Ma (mid Early Cretaceous). This estimate was robust to alternative analyses changing core assumptions. With 994 genera, this tree provides a comprehensive source of secondary calibrations for studies on butterflies.
Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis
Authors: Li Jin , Yu Peng 
Published: February 2018

AbstractPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For understanding the mechanism of psoriasis, though, alternative splicing analysis has received relatively little attention in the field. Here, we developed and applied several computational analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential alternative splicing analyses detected hundreds of differential alternative splicing changes. Our analysis of conservation revealed many exon-skipping events conserved between mice and humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. Three of the nine splicing factors were confirmed upon analyzing the human data. Our computational methods have generated predictions for the potential role of splicing in psoriasis. Future experiments on the novel candidates predicted by our computational analysis are expected to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for new therapeutic treatments.
Time efficient preparation methods for MRI brain scanning in awake young children and factors associated with success
Authors: Thieba Camilia , Frayne Ashleigh , Walton Matthew , Mah Alyssa , Benischek Alina , Dewey Deborah , Lebel Catherine 
Published: February 2018

AbstractObjectiveYoung children are often unable to remain still for magnetic resonance imaging (MRI). Various preparation methods have been reported to avoid sedation or anesthesia, with mixed success rates and feasibility. Here we describe a time-efficient preparation method and factors associated with successful scanning in young chdilren.We recruited 134 children aged 2.0–5.0 years for an MRI study. Some children completed a training session on a mock scanner, and all children received a 15–20 minute introduction to scanning procedures immediately before their scan. We compared success between children receiving mock scanner training or not, and evaluated demographic or cognitive factors that predicted success.Results97 children (72%) completed at least one sequence successfully; 64 children provided high-quality data for all 3 sequences. Cognitive scores were higher in successful children, but children who received mock scanner training were less likely to be successful. A case-controlled comparison of children matched on age, gender, and cognitive scores found no differences between children receiving training or not.We present a quick method for preparing young children for awake MRI scans. Our data suggests limited advantages of mock scanner preparation for healthy young children, and that cognitive abilities may help predict success.
The H3K9 methyltransferase SETDB1 maintains female identity inDrosophilagerm cells by repressing expression of key spermatogenesis genes
Authors: Smolko Anne E. , Shapiro-Kulnane Laura , Salz Helen K. 
Published: February 2018

AbstractThe preservation of germ cell sexual identity is essential for gametogenesis. Here we show that H3K9me3-mediated gene silencing is integral to female fate maintenance inDrosophilagerm cells. Germ cell-specific loss of the H3K9me3 pathway members, the trimethyltransferase SETDB1, its binding partner WDE, and the H3K9 binding protein HP1a, cause the inappropriate expression of testis genes. SETDB1 is required for H3K9me3 accumulation on a select subset of the silenced testis genes. Interestingly, these SETDB1-dependent H3K9me3 domains are highly localized and do not spread into neighboring loci. Regional deposition is especially striking at thephf7locus, a key regulator of male germ cell sexual fate.phf7is primarily regulated by alternative promoter usage and transcription start site (TSS) selection. We find H3K9me3 accumulation is restricted to the silenced testis-specific TSS region in ovaries. Furthermore, its recruitment tophf7and repression of the testis-specific transcript is dependent on the female sex determination geneSxl. These findings demonstrate that female identity is secured by a pathway in whichSxlis the upstream female-specific regulator, SETDB1 is the required chromatin writer andphf7is one of the critical SETDB1 target genes. This function of SETDB1 is unrelated to its canonical role in piRNA biogenesis and silencing of transposable elements. Collectively our findings support a novel model in which female fate is preserved by deposition of H3K9me3 repressive marks on key spermatogenesis genes and suggest that this strategy for securing cell fate may be widespread.
GITAR: an Open Source Tool for Analysis and Visualization of Hi-C Data
Authors: Calandrelli Riccardo , Wu Qiuyang , Guan Jihong , Zhong Sheng 
Published: February 2018

AbstractInteractions between chromatin segments play a large role in functional genomic assays and developments in genomic interaction detection methods have shown interacting topological domains within the genome. Among these methods, Hi-C plays a key role. Here, we present GITAR (Genome Interaction Tools and Resources), a software to perform a comprehensive Hi-C data analysis, including data preprocessing, normalization, visualization and topologically associated domains (TADs) analysis. GITAR is composed of two main modules: 1) HiCtool, a Python library to process and visualize Hi-C data, including TADs analysis and 2) Processed data library, a large collection of human and mouse datasets processed using HiCtool. HiCtool leads the user step-by-step through a pipeline which goes from the raw Hi-C data to the computation, visualization and optimized storage of intra-chromosomal contact matrices and topological domain coordinates. A large collection of standardized processed data allows to compare different datasets in a consistent way and it saves time of work to obtain data for visualization or additional analyses. GITAR enables users without any programming or bioinformatic expertise to work with Hi-C data and it is freely available for the public at http://genomegitar.org as an open source software.
Cold shock as a screen for genes involved in cold acclimatization in Neurospora crassa
Authors: Watters Michael K. , Manzanilla Victor , Howell Holly , Mehreteab Alexander , Rose Erik , Walters Nicole , Seitz Nicholas , Nava Jacob , Kekelik Sienna , Knuth Laura , Scivinsky Brianna 
Published: February 2018

ABSTRACTWhen subjected to rapid drops of temperature (cold shock), Neurospora responds with a dramatic, but temporary shift in its branching pattern. While the cold shock response has been described morphologically, it has yet to be examined genetically. This project aims to begin the genetic characterization of the cold shock response and the associated acclimatization to cold environments. We report here the results of a screen of mutants from the Neurospora knockout library for alterations in their morphological response to cold shock and thus, their ability to acclimatize to the cold. Three groups of knockouts were selected to be subject to this screen: genes previously suspected to be involved in hyphal development as well as knockouts resulting in morphological changes; transcription factors; and genes homologous to E. coli genes known to alter their expression in response to cold shock. Several strains were identified with altered responses. The genes impacted in these mutants are listed and discussed. A significant percentage (81%) of the knockouts of genes homologous to those previously identified in E. coli showed altered cold shock responses in Neurospora – suggesting that the response in these two organisms is largely shared in common.