bluuebunny/crossref_metadata_2025_split huggingface dataset:
Girls’ attentive traits associate with cerebellar to dorsal attention and default mode network connectivity
Authors: Rohr Christiane S. , Dimond Dennis , Schuetze Manuela , Cho Ivy Y. K. , Lichtenstein-Vidne Limor , Okon-Singer Hadas , Dewey Deborah , Bray Signe 
Published: December 2018

ABSTRACTAttention traits are a cornerstone to the healthy development of children’s performance in the classroom, their interactions with peers, and in predicting future success and problems. The cerebellum is increasingly appreciated as a region involved in complex cognition and behavior, and moreover makes important connections to key brain networks known to support attention: the dorsal attention and default mode networks (DAN; DMN). The cerebellum has also been implicated in childhood disorders affecting attention, namely autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), suggesting that attention networks extending to the cerebellum may be important to consider in relation to attentive traits. Yet, direct investigations into the association between cerebellar FC and attentive traits are lacking. Therefore, in this study we examined attentive traits, assessed using parent reports of ADHD and ASD symptoms, in a community sample of 52 girls aged 4-7 years, i.e. around the time of school entry, and their association with cerebellar connections with the DAN and DMN. We found that cortico-cerebellar functional connectivity (FC) jointly and differentially correlated with attentive traits, through a combination of weaker and stronger FC across anterior and posterior DAN and DMN nodes. These findings suggest that cortico-cerebellar integration may play an important role in the manifestation of attentive traits.
Intravital optoacoustic ultrasound bio-microscopy reveals radiation-inhibited skull angiogenesis
Authors: Estrada Héctor , Rebling Johannes , Sievert Wolfgang , Hladik Daniela , Hofmann Urs , Gottschalk Sven , Tapio Soile , Multhoff Gabriele , Razansky Daniel 
Published: December 2018

AbstractAngiogenesis is critical in bone development and growth. Dense, large-scale, and multi-layered vascular networks formed by thin-walled sinusoidal vessels perfuse the plate bones and play an important role in bone repair. Yet, the intricate functional morphology of skull microvasculature remains poorly understood as it is difficult to visualize using existing intravital microscopy techniques. Here we introduced an intravital fully-transcranial imaging approach based on hybrid optoacoustic and ultrasound bio-microscopy, allowing for large-scale observations and quantitative analysis of the vascular morphology, angiogenesis, vessel remodeling, and subsurface roughness in murine skulls. Our approach also enabled high-throughput physiological studies to understand radiation-inhibited angiogenesis in the skull bone. We observed previously undocumented sinusoidal vascular networks spanning the entire skullcap, thus opening new vistas for studying the complex interactions between calvarian, pial, and cortical vascular systems.
OncodriveCLUSTL: a sequence-based clustering method to identify cancer drivers
Authors: Arnedo-Pac Claudia , Mularoni Loris , Muiños Ferran , Gonzalez-Perez Abel , Lopez-Bigas Nuria 
Published: December 2018

AbstractSummaryThe identification of the genomic alterations driving tumorigenesis is one of the main goals in oncogenomics research. Given the evolutionary principles of cancer development, computational methods that detect signals of positive selection in the pattern of tumor mutations have been effectively applied in the search for cancer genes. One of these signals is the abnormal clustering of mutations, which has been shown to be complementary to other signals in the detection of driver genes. We have developed OncodriveCLUSTL, a new sequence-based clustering algorithm to detect significant clustering signals across genomic regions. OncodriveCLUSTL is based on a local background model derived from the simulation of mutations accounting for the composition of tri- or penta-nucleotide context substitutions observed in the cohort under study. Our method is able to identify known clusters and bona-fide cancer drivers across cohorts of tumor whole-exomes, outperforming the existing OncodriveCLUST algorithm and complementing other methods based on different signals of positive selection. We show that OncodriveCLUSTL may be applied to the analysis of non-coding genomic elements and non-human mutations data.Availability and implementationOncodriveCLUSTL is available as an installable Python 3.5 package. The source code and running examples are freely available at https://bitbucket.org/bbglab/oncodriveclustl under GNU Affero General Public License.Contactnuria.lopez@irbbarcelona.org
Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching
Authors: Wan Ruixue , Bai Rui , Yan Chuangye , Lei Jianlin , Shi Yigong 
Published: December 2018

SummaryPre-mRNA splicing is executed by the spliceosome. Structural characterization of the catalytically activated complex (B*) is pivotal for mechanistic understanding of catalysis of the branching reaction by the spliceosome. In this study, we assembled the B* complex on two different pre-mRNAs from Saccharomyces cerevisiae and determined the cryo-EM structures of four distinct B complexes at overall resolutions of 2.9-3.8 Å. The duplex between U2 snRNA and the branch point sequence (BPS) is located 13-20 Å away from the 5’-splice site (5’SS) in the B* complexes that are devoid of the step I splicing factors Yju2 and Cwc25. Recruitment of Yju2 into the active site brings the U2/BPS duplex into the vicinity of 5’SS, ready for branching. In the absence of Cwc25, the nucleophile from BPS is positioned about 4 Å away from, and remains to be activated by, the catalytic metal M2. This analysis reveals the functional mechanism of Yju2 and Cwc25 in branching. These four structures constitute compelling evidence for substrate-specific conformations of the spliceosome in a major functional state.
Selective peak inference: Unbiased estimation of raw and standardized effect size at local maxima
Authors: Davenport Samuel J. , Nichols Thomas E. 
Published: December 2018

AbstractThe spatial signals in neuroimaging mass univariate analyses can be characterized in a number of ways, but one widely used approach is peak inference: the identification of peaks in the image. Peak locations and magnitudes provide a useful summary of activation and are routinely reported, however, the magnitudes reflect selection bias as these points have both survived a threshold and are local maxima. In this paper we propose the use of resampling methods to estimate and correct this bias in order to estimate both the raw units change as well as standardized effect size measured with Cohen’sdand partialR2. We evaluate our method with a massive open dataset, and discuss how the corrected estimates can be used to perform power analyses.
The Landscape Of Circular RNA Expression In The Human Brain
Authors: Gokoolparsadh Akira , Anwar Firoz , Voineagu Irina 
Published: December 2018

ABSTRACTCircular RNAs (circRNAs) are enriched in the mammalian brain and are upregulated in response to neuronal differentiation and depolarisation. These RNA molecules, formed by non-canonical back-splicing, have both regulatory and translational potential. Here, we carried out an extensive characterisation of circRNA expression in the human brain, in nearly two hundred human brain samples, from both healthy individuals and autism cases. We identify hundreds of novel circRNAs and demonstrate that circRNAs are not expressed stochastically, but rather as major isoforms. We characterise inter-individual variability of circRNA expression in the human brain and show that inter-individual variability is less pronounced than variability between cerebral cortex and cerebellum. We also find that circRNA expression is dynamic during cellular maturation in brain organoids, but remains largely stable across the adult lifespan. Finally, we identify a circRNA co-expression module upregulated in autism samples, thereby adding another layer of complexity to the transcriptome changes observed in autism brain. These data provide a comprehensive catalogue of circRNAs as well as a deeper insight into their expression in the human brain, and are available as a free resource in browsable format at: http://www.voineagulab.unsw.edu.au/circ_rna
Proteomic Analyses of Morphological Variants ofBorrelia burgdorferiShed New Light on Persistence Mechanisms: Implications for Pathogenesis, Diagnosis and Treatment
Authors: Feng Jie , Zhang Ying 
Published: December 2018

AbstractBorrelia burgdorfericauses Lyme disease, which is the most common vector borne disease in the United States and Europe. Although 2-4 week antibiotic treatment for Lyme disease is effective in the majority of cases, about 10–20% patients suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the mechanisms of PTLDS are unclear, persisting organisms not killed by current Lyme antibiotics has been suggested as a possible explanation.B. burgdorferican spontaneously develop different morphological variant forms under stress or in stationary phase with increased persistence to antibiotics. To shed light on the possible mechanisms by which these variant forms develop persistence, here, we isolated threeB. burgdorferiforms, log phase spirochetal form, stationary phase planktonic form, and stationary phase aggregated biofilm-like microcolony form. We showed that the two separated stationary phase forms especially microcolony form have more persistence to antibiotics than the log phase spirochetal form. Then, we performed mass spectrometry (MS/MS) analysis to determine the proteomic profiles of the three different forms to reveal the mechanisms of persistence inB. burgdorferi. We identified 1023 proteins in the threeB. burgdorferiforms, with 642 proteins (63%) differentially expressed. Compared with the log phase spirochetal form ofB. burgdorferi, a total of 143 proteins were upregulated in both stationary phase planktonic form and microcolony form. Among these common upregulated proteins, 90 proteins had predicted functions and were mapped to different pathways involved in infection and virulence, DNA repair, heat shock, transport, sporulation, cell envelope and metabolism, many of which are consistent with persister mechanisms in other bacteria. A particularly interesting observation is that infection and virulence related proteins are highly up-regulated in stationary phase planktonic form and microcolony form compared with log phase spirochetal form. These findings shed new light on the mechanisms ofB. burgdorferipersistence and offer novel targets for developing more effective diagnostics, vaccines and treatments.
Nucleotide Archival Format (NAF) enables efficient lossless reference-free compression of DNA sequences
Authors: Kryukov Kirill , Ueda Mahoko Takahashi , Nakagawa So , Imanishi Tadashi 
Published: December 2018

AbstractSummaryDNA sequence databases use compression such as gzip to reduce the required storage space and network transmission time. We describe Nucleotide Archival Format (NAF) – a new file format for lossless reference-free compression of FASTA and FASTQ-formatted nucleotide sequences. NAF compression ratio is comparable to the best DNA compressors, while providing dramatically faster decompression. We compared our format with DNA compressors: DELIMINATE and MFCompress, and with general purpose compressors: gzip, bzip2, xz, brotli, and zstd.AvailabilityNAF compressor and decompressor, as well as format specification are available at https://github.com/KirillKryukov/naf. Format specification is in public domain. Compressor and decompressor are open source under the zlib/libpng license, free for nearly any use.Contactkkryukov@gmail.com
Using ribosome profiling to quantify differences in protein expression: a case study in Saccharomyces cerevisiae oxidative stress conditions
Authors: Blevins William R. , Tavella Teresa , Moro Simone G. , Blasco-Moreno Bernat , Closa-Mosquera Adrià , Díez Juana , Carey Lucas B. , Albà M. Mar 
Published: December 2018

AbstractCells respond to changes in the environment by modifying the concentration of specific proteins. Paradoxically, the cellular response is usually examined by measuring variations in transcript abundance by high throughput RNA sequencing (RNA-Seq), instead of directly measuring protein concentrations. This happens because RNA-Seq-based methods provide better quantitative estimates, and more extensive gene coverage, than proteomics-based ones. However, variations in transcript abundance do not necessarily reflect changes in the corresponding protein abundance. How can we close this gap? Here we explore the use of ribosome profiling (Ribo-Seq) to perform differentially gene expression analysis in a relatively well-characterized system, oxidative stress in baker’s yeast. Ribo-Seq is an RNA sequencing method that specifically targets ribosome-protected RNA fragments, and thus is expected to provide a more accurate view of changes at the protein level than classical RNA-Seq. We show that gene quantification by Ribo-Seq is indeed more highly correlated with protein abundance, as measured from mass spectrometry data, than quantification by RNA-Seq. The analysis indicates that, whereas a subset of genes involved in oxidation-reduction processes is detected by both types of data, the majority of the genes that happen to be significant in the RNA-Seq-based analysis are not significant in the Ribo-Seq analysis, suggesting that they do not result in protein level changes. The results illustrate the advantages of Ribo-Seq to make inferences about changes in protein abundance in comparison with RNA-Seq.
CRUP: A comprehensive framework to predict condition-specific regulatory units
Authors: Ramisch Anna , Heinrich Verena , Glaser Laura V. , Fuchs Alisa , Yang Xinyi , Benner Philipp , Schöpflin Robert , Li Na , Kinkley Sarah , Hillmann Anja , Longinotto John , Heyne Steffen , Czepukojc Beate , Kessler Sonja M. , Kiemer Alexandra K. , Cadenas Cristina , Arrigoni Laura , Gasparoni Nina , Manke Thomas , Pap Thomas , Pospisilik Andrew , Hengstler Jan , Walter Jörn , Meijsing Sebastiaan H. , Chung Ho-Ryun , Vingron Martin 
Published: December 2018

AbstractWe present the software CRUP (Condition-specific Regulatory Units Prediction) to infer from epigenetic marks a list of regulatory units consisting of dynamically changing enhancers with their target genes. The workflow consists of a novel pre-trained enhancer predictor that can be reliably applied across cell lines and species, solely based on histone modification ChIP-seq data. Enhancers are subsequently assigned to different conditions and correlated with gene expression to derive regulatory units. We thoroughly test and then apply CRUP to a rheumatoid arthritis model, identifying enhancer-gene pairs comprising known disease genes as well as new candidate genes.Availabilityhttps://github.com/VerenaHeinrich/CRUP
Cyclin A triggers Mitosis either via Greatwall or Cyclin B
Authors: Hégarat Nadia , Crncec Adrijana , Peredoa Rodri-guez Maria F. Suarez , Iturra Fabio Echegaray , Gu Yan , Lang Paul F. , Barr Alexis R. , Bakal Chris , Kanemaki Masato T. , Lamond Angus I. , Novak Bela , Ly Tony , Hochegger Helfrid 
Published: December 2018

AbstractTwo mitotic Cyclins, A and B, exist in higher eukaryotes, but their specialised functions in mitosis are poorly understood. Using degron tags we analyse how acute depletion of these proteins affects mitosis. Loss of Cyclin A in G2-phase prevents the initial activation of Cdk1. Cells lacking Cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phos-phatase inactivation by Greatwall kinase. The final barrier to mitotic establishment corresponds to nuclear envelope breakdown that requires a decisive shift in the balance of Cdk1 and PP2A:B55 activity. Beyond this point Cyclin B/Cdk1 is essential to phosphorylate a distinct subset mitotic Cdk1 substrates that are essential to complete cell division. Our results identify how Cyclin A, B and Greatwall coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phos-phorylation.
High-flow Nano-chromatography Columns Facilitate Rapid and High-quality Proteome Analysis on Standard Nano-LC Hardware
Authors: Hughes Christopher S. , Adomat Hans , LeBihan Stephane , Collins Colin , Sorensen P.H. , Morin Gregg B. 
Published: December 2018

AbstractOptimizing the acquisition of proteomics data collected from a mass spectrometer (MS) requires careful selection of processed material quantities, liquid-chromatography (LC) setup, and data acquisition parameters. The small internal diameter (ID) columns standardly used in nano-chromatography coupled MS result in long per injection overhead times that require sacrifices in design of offline-fractionation and data acquisition schemes. As cohort sizes and the numbers of samples to be analyzed continue to increase, there is a need to investigate methods for improving the efficiency and time of an acquisition (LC + MS). In this work, the ability to improve throughput in single runs or as part of an in-depth proteome analysis of a fractionated sample using standard LC hardware is investigated. Capitalizing on the increased loading capacity of nanochromatography columns with larger IDs, substantially improved throughput with no reduction in detection sensitivity is achieved in single-injection proteome analyses. An optimized 150 μm ID column setup is paired with an offline fractionation-concatenation scheme to demonstrate the ability to perform in-depth proteome analysis on-par with current state-of-the-art studies, while minimizing sample loading overhead. Together, these data demonstrate an easy and effective means to improve sample analysis throughput with no reduction in data quality using an approach that is applicable to any standard nano-LC hardware.
Decoys provide a scalable platform for the genetic analysis of plant E3 ubiquitin ligases that regulate circadian clock function
Authors: Feke Ann , Liu Wei , Hong Jing , Li Man-Wah , Lee Chin-Mei , Zhou Elton , Gendron Joshua M. 
Published: December 2018

ABSTRACTThe circadian clock in all eukaryotes relies on the regulated degradation of clock proteins to maintain 24-hour rhythmicity. Despite this knowledge, we know very few of the components that mediate degradation of proteins to control clock function. This is likely due to high levels of gene duplication and functional redundancy within plant E3 ubiquitin ligase gene families. In order to overcome this issue and discover E3 ubiquitin ligases that control circadian clock function, we generated a library of transgenic Arabidopsis lines expressing dominant-negative “decoy” E3 ubiquitin ligases. We determined their effects on the plant circadian clock and identified dozens of new potential regulators of circadian clock function. To demonstrate the potency of the decoy screening methodology to overcome genetic redundancy and identify bona fide clock regulators, we performed follow-up studies on PUB59 and PUB60. Using knock-out studies, we show that they redundantly control circadian clock period by regulating gene splicing. Furthermore, we confirm that they are part of a conserved protein complex that mediates splicing in eukaryotes. This work demonstrates the viability of E3 ubiquitin ligase decoys as a scalable screening platform to overcome traditional genetic challenges and discover E3 ubiquitin ligases that regulate plant developmental processes.
Functional and evolutionary impact of polymorphic inversions in the human genome
Authors: Giner-Delgado Carla , Villatoro Sergi , Lerga-Jaso Jon , Gayà-Vidal Magdalena , Oliva Meritxell , Castellano David , Pantano Lorena , Bitarello Bárbara D. , Izquierdo David , Noguera Isaac , Olalde Iñigo , Delprat Alejandra , Blancher Antoine , Lalueza-Fox Carles , Esko Tõnu , O’Reilly Paul , Andrés Aida , Ferretti Luca , Puig Marta , Cáceres Mario 
Published: December 2018

SUMMARYInversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about inversions in the human genome due to the difficulty of their detection. Here, thanks to the development of a new high-throughput genotyping method, we have performed a complete study of a representative set of 45 common human polymorphic inversions. Most inversions promoted by homologous recombination occur recurrently both in humans and great apes and, since they are not tagged by SNPs, they are missed by genome-wide association studies. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.
Visualizing murine placental extracellular vesicle data with tidyNano: a computational framework for analyzing and visualizing nanoparticle data in R
Authors: Nguyen Sean L , Greenberg Jacob W , Wang Hao , Collaer Benjamin W , Wang Jianrong , Petroff Margaret G 
Published: December 2018

AbstractExtracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication, and in mammals are generally classified as ~50–150nm exosomes, ~100–1000nm microvesicles, and apoptotic bodies, each arising as a result of different biological processes. EVs carry protein, lipids, and nucleic acids within the circulation, to target cells whereupon they mediate physiological changes. Due to their small size, quantification and characterization by conventional microscopy is not possible. However, nanoparticle tracking analysis (NTA) has provided a method to determine the fluid concentration and size of extracellular vesicles and other nanoparticles. While NTA provides statistical summaries of samples in an experiment, a recurring difficulty is the organization, manipulation, and management of raw particle count data because of the large size of datasets, and resultant vulnerability to user error. To address these limitations, we developed tidyNano, an R package that provides functions to import, clean, and quickly summarize raw NanoSight (Malvern Panalytical) data for efficient calculation of statistics and visualization. Here, we provide a framework for importing raw nanoparticle data and provide functions to facilitate rapid and efficient analysis, visualization and calculation of summary statistics. tidyNano was used to analyze murine plasma extracellular vesicles across gestation by aggregating and summarizing samples based on technical, biological and gestational parameters. In addition, we developed shinySIGHT, a Shiny web application that allows for interactive exploration and visualization of EV data. Using this package, we analyzed data generated from 36 samples of EV derived from the plasma of mice across gestation.Peripheral EV concentration increased linearly across pregnancy, with trending increases as early as gestation day (GD) 5.5 and significant rises at GD14.5, and 17.5 relative to EV concentrations in nonpregnant females. Thus, the data highlight the utility of the mouse as a model of EV biology in pregnancy. Further, the package provides a mechanism for seamless analysis of EV data generated by NanoSight. Importantly, this package provides a straightforward framework by which diverse types of large datasets can be simply and efficiently analyzed. tidyNano and shinySIGHT are freely available under the MIT license and is hosted on GitHub (https://nguyens7.github.io/tidyNano/).