bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCFold: rapid and accurate prediction of coiled-coil structures and application to modelling intermediate filaments
Authors: Guzenko Dmytro , Strelkov Sergei V. 
Published: April 2017

AbstractAccurate molecular structure of the protein dimer representing the elementary building block of intermediate filaments (IFs) is essential towards the understanding of the filament assembly, rationalizing their mechanical properties and explaining the effect of disease-related IF mutations. The dimer contains a ∼300-residue longα-helical coiled coil which is not assessable to either direct experimental structure determination or modelling using standard approaches. At the same time, coiled coils are well-represented in structural databases. Here we present CCFold, a generally applicable threading-based algorithm which produces coiled-coil models from protein sequence only. The algorithm is based on a statistical analysis of experimentally determined structures and can handle any hydrophobic repeat patterns in addition to the most common heptads. We demonstrate that CCFold outperforms general-purpose computational folding in terms of accuracy, while being faster by orders of magnitude. By combining the CCFold algorithm and Rosetta folding we generate representative dimer models for all IF protein classes. The source code is freely available athttps://github.com/biocryst/IF
PB-kPRED: knowledge-based prediction of protein backbone conformation using a structural alphabet
Authors: Vetrivel Iyanar , Mahajan Swapnil , Tyagi Manoj , Hoffmann Lionel , Sanejouand Yves-Henri , Srinivasan Narayanaswamy , de Brevern Alexandre G. , Cadet Frédéric , Offmann Bernard 
Published: April 2017

AbstractLibraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks (PBs), is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of PBs. Thus, predicting the local structure of a protein in terms of protein blocks is a step towards the objective of predicting its 3-D structure. Here a new approach, kPred, is proposed towards this aim that is independent of the evolutionary information available. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) apply a purely knowledge-based algorithm, not relying on secondary structure predictions or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures.Based on the strategy used for scanning the database, the method was able to achieve efficient mean Q16accuracies between 40.8% and 66.3% for a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. The impact of these scanning strategies on the prediction was evaluated and is discussed. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2of 0.82). An online version of the tool is provided freely for non-commercial usage athttp://www.bo-protscience.fr/kpred/.
High accuracy label-free classification of kinetic cell states from holographic cytometry
Authors: Hejna Miroslav , Jorapur Aparna , Song Jun S. , Judson Robert L. 
Published: April 2017

AbstractDigital holographic microscopy permits live and label-free visualization of adherent cells. Here we report the application of this approach for high accuracy kinetic quantitative cytometry. We identify twenty-six label-free optical and morphological features that are biologically independent. When used as a basis for machine learning, these features allow blind single cell classification with up to 95% accuracy. We present methods to control for inherent holographic noise, thereby establishing a set of reliable quantitative features. Together, these contributions permit continuous digital holographic cytometry for three or more days. Applying our approach to human melanoma cells treated with a panel of cancer therapeutics, we can track the response of each cell, simultaneously classifying multiple behaviors such as cell cycle length, motility, apoptosis, senescence, and heterogeneity of response to each therapeutic. Importantly, we demonstrate relationships between these phenotypes over time. This work thus provides an experimental and computational roadmap for low cost live-cell imaging and kinetic classification of heterogeneous adherent cell populations.
ChIPWig: A Random Access-Enabling Lossless and Lossy Compression Method for ChIP-seq Data
Authors: Ravanmehr Vida , Kim Minji , Wang Zhiying , Milenković Olgica 
Published: April 2017

AbstractMotivationThe past decade has witnessed a rapid development of data acquisition technologies that enable integrative genomic and proteomic analysis. One such technology is chromatin immunoprecipitation sequencing (ChIP-seq), developed for analyzing interactions between proteins and DNA via next-generation sequencing technologies. As ChIP-seq experiments are inexpensive and time-efficient, massive datasets from this domain have been acquired, introducing significant storage and maintenance challenges. To address the resulting Big Data problems, we propose a state-of-the-art lossless and lossy compression framework specifically designed for ChIP-seq Wig data, termed ChIPWig. Wig is a standard file format, which in this setting contains relevant read density information crucial for visualization and downstream processing. ChIPWig may be executed in two different modes: lossless and lossy. Lossless ChIPWig compression allows for random access and fast queries in the file through careful variable-length block-wise encoding. ChIPWig also stores the summary statistics of each block needed for guided access. Lossy ChIPWig, in contrast, performs quantization of the read density values before feeding them into the lossless ChIPWig compressor. Nonuniform lossy quantization leads to further reductions in the file size, while maintaining the same accuracy of the ChIP-seq peak calling and motif discovery pipeline based on the NarrowPeaks method tailor-made for Wig files. The compressors are designed using new statistical modeling approaches coupled with delta and arithmetic encoding.ResultsWe tested the ChIPWig compressor on a number of ChIP-seq datasets generated by the ENCODE project. Lossless ChIPWig reduces the file sizes to merely 6% of the original, and offers an average 6-fold compression rate improvement compared to bigWig. The running times for compression and decompression are comparable to those of bigWig. The compression and decompression speed rates are of the order of 0.2 MB/sec using general purpose computers. ChIPWig with random access only slightly degrades the performance and running time when compared to the standard mode. In the lossy mode, the average file sizes reduce by 2-fold compared to the lossless mode. Most importantly, near-optimal nonuniform quantization with respect to mean-square distortion does not affect peak calling and motif discovery results on the data tested.Availability and ImplementationSource code and binaries freely available for download athttps://github.com/vidarmehr/ChIPWigContactmilenkov@illinois.eduSupplementary informationIs available on bioRxiv.
Predation of stocked salmon by riparian wildlife in semi-natural stream
Authors: Miyamoto Kouta , Squires Theodore E. , Araki Hitoshi 
Published: April 2017

AbstractPredation after release is one of the major concerns of hatchery fish conservation and propagation. However, the relationship among the size of hatchery fish, the predator species, and their behaviors in natural environments is largely unknown. To understand the relationship, we conducted predation experiments in outdoor tanks and a semi-natural stream with exposure to local predators. Two different ranges of fork lengths of masu salmon (Oncorhynchus masou) were examined as prey sizes. Camera trap data showed that grey herons (Ardea cinerea) were the primary predator animal in the system, and that most herons utilized shallow areas in the morning or evening. Increasing the density of stocked salmon brought in more grey herons. More importantly, predation by grey herons resulted in the survival rate of larger salmon being significantly lower than that of the smaller salmon. Our results suggest that it is important to understand local predators, adjust the optimum body size of hatchery fish at release, and choose the appropriate stocking site and time of day for maximizing the effectiveness of fish stocking.
Direct conversion of human fibroblasts into osteoblasts and osteocytes with small molecules and a single factor, Runx2
Authors: Li Yanjiao , Wang YaoLong , Yu Juehua , Ma Zhaoxia , Bai Qiong , Wu Xingfei , Bao Pengfei , Li Lirong , Ma Daiping , Liu Jinxue , Liu Change , Chen Fangyun , Hu Min 
Published: April 2017

AbstractHuman osteoblasts can be induced from somatic cells by introducing defined factors, however, the strategy limits cells therapeutic applications for its multi-factor and complicated genetic manipulations that may bring uncertainty into the genome. Another important cell type in bone metabolism, osteocytes, which play a central role in regulating the dynamic nature of bone in all its diverse functions, have not been obtained from transdifferetiation so far. Herein, we have established procedures to convert human fibroblast directly into osteocyte-like and osteoblast-like cells using a single transcription factor, Runx2 and chemical cocktails by activating Wnt and cAMP/PKA pathways. These induced osteoblast-like cells express osteogenic markers and generate mineralized nodule deposition. A good performance of bone formation from these cells was observed in subcutaneous site of mouse at 4 weeks post-transplantation. Moreover, further studies convert human fibroblasts into osteocyte-like cells by orchestrating timing of the aforementioned chemical cocktails exposure. These osteocyte-like cells express osteocyte-specific markers and display characteristic morphology features of osteocytes. In summary, this study provides a promising strategy for cell-based therapy in bone regenerative medicine by direct reprogramming of fibroblasts into osteocytes and osteoblasts.
The diversity, structure and function of heritable adaptive immunity sequences in the Aedes aegypti genome
Authors: Whitfield Zachary J. , Dolan Patrick T. , Kunitomi Mark , Tassetto Michel , Seetin Matthew G. , Oh Steve , Heiner Cheryl , Paxinos Ellen , Andino Raul 
Published: April 2017

AbstractThe Aedes aegypti mosquito is a major vector for arboviruses including dengue, chikungunya and Zika virus. Combating the spread of these viruses requires a more complete understanding of the mosquito immune system. Recent studies have implicated genomic endogenous viral elements (EVEs) derived from non-retroviral RNA viruses in insect immunity. Because these elements are inserted into repetitive regions of the mosquito genome, their large-scale structure and organization with respect to other genomic elements has been difficult to resolve with short-read sequencing. To better define the origin, diversity and biological role of EVEs, we employed single-molecule, real-time sequencing technology to generate a high quality, long-read assembly of the Ae. aegypti-derived Aag2 cell line genome. We leverage the quality and contiguity of this assembly to characterize the diversity and genomic context of EVEs in the genome of this important model system. We find that EVEs in the Aag2 genome are acquired through recombination by LTR retrotransposons, and organize into larger loci (>50kbp) characterized by high LTR density. These EVE containing loci are associated with increased transcription factor binding sight density and increased production of anti-genomic piRNAs. We also detected piRNA processing corresponding to on-going viral infection. This global view of EVEs and piRNA responses demonstrates the ubiquity and diversity of these heritable elements that define small-RNA mediated antiviral immunity in mosquitoes.
Characterization of the stoichiometry of the complex formed by Staphylococcal LukSF and human C5aR receptor in living cells
Authors: Haapasalo Karita , Wollman Adam J.M , de Haas Carla , van Kessel Kok , van Strijp Jos , Leake Mark C. 
Published: April 2017

SUMMARYStaphylococcus aureusPanton Valentine Leukocidin (PVL) is a pore-forming toxin comprising protein subunits LukS and LukF. Binding of LukS to human C5a receptor (hC5aR) on leukocytes induces secondary binding of LukF and assembly of lytic complexes. Previous analysis suggests that PVL consists of 4-plus-4 LukS/LukF subunits but the exact stoichiometry between LukS, LukF and hC5aR is not yet known. In this study we determine the stoichiometry and spatiotemporal dynamics of functional LukS/LukF-hC5aR complexes in living eukaryotic cells. By using rapid total internal reflection fluorescence (TIRF) and single-molecule photobleaching analysis we found that tetrameric LukS-hC5aR complexes are formed within a cluster of receptors. Upon binding to hC5aR each LukS subunit binds LukF leading to lytic pore formation and simultaneous dissociation of receptors from the complex. Our findings corroborate a hetero-octamer model but provide a new view on the kinetics of crucial virulence factor assembly on integrated host cell membrane receptors.
Topological demarcation by HMGB2 is disrupted early upon senescence entry across cell types and induces CTCF clustering
Authors: Zirkel Anne , Nikolic Milos , Sofiadis Konstantinos , Mallm Jan-Philipp , Brant Lilija , Becker Christian , Altmüller Janine , Franzen Julia , Koker Mirjam , Gusmao Eduardo G , Costa Ivan G , Ullrich Roland T , Wagner Wolfgang , Nürnberg Peter , Rippe Karsten , Papantonis Argyris 
Published: April 2017

AbstractAgeing-relevant processes, like cellular senescence, are characterized by complex, often stochastic, events giving rise to heterogeneous cell populations. We hypothesized that entry into senescence of different primary human cells can be triggered by one early molecular event affecting the spatial organization of chromosomes. To test this, we combined whole-genome chromosome conformation capture, population and single-cell transcriptomics, super-resolution imaging, and functional analyses applied on proliferating and replicatively-senescent populations from three distinct human cell types. We found a number of genes involved in DNA conformation maintenance being suppressed upon senescence across cell types. Of these, the abundant high mobility group (HMG) B1 and B2 nuclear factors are quantitatively removed from cell nuclei before typical senescence markers appear, and mark a subset of topologically-associating domain (TAD) boundaries. Their loss coincides with obvious reorganization of chromatin interactions via the dramatic spatial clustering of CTCF foci. HMGB2 knock-down recapitulates this senescence-induced CTCF clustering, while also affecting insulation at TAD boundaries. We accordingly propose that HMGB-mediated deregulation of chromosome conformation constitutes a primer for the ensuing senescent program across cell types.
Model based safety ranking of opioid drugs using Adversity index
Authors: Asvalayana Krishna , Ghubade Samadhan , Paranjpe Sharayu , Gore Anil 
Published: April 2017

AbstractAnnual ADR report counts of opioid drugs are examined to develop a candidate index of overall safety of a drug. Actual counts for various drugs have been sourced fromwww.vigiaccess.org. A feature found to be common to all drugs considered is that an exponential function adequately describes the pattern of cumulative counts. In the exponential model, the parameter in the exponent (rate constant) is robust and remains the same whether counts are corrected for exposure or not. We propose use of this rate constant as ‘adversity index’ of a drug. Drugs in use can be ranked by value of adversity index, lower value suggesting safer drug.Key pointsCumulative total of annual ADR report counts of opioid drugs follows an exponential pattern. Rate constant in the model is independent of volume of use of the drug. Hence it is a suitable index of overall safety.
MaxTiC: Fast ranking of a phylogenetic tree by Maximum Time Consistency with lateral gene transfers
Authors: Chauve Cédric , Rafiey Akbar , Davín Adrián A. , Scornavacca Celine , Veber Philippe , Boussau Bastien , Szöllősi Gergely J. , Daubin Vincent , Tannier Eric 
Published: April 2017

AbstractLateral gene transfers between ancient species contain information about the relative timing of species diversification. Specifically, the ancestors of a donor species must have existed before the descendants of the recipient species. Hence, the detection of a transfer event can be translated into a time constraint between nodes of a phylogeny if the donor and recipient can be identified. When a set of transfers is detected by interpreting the phylogenetic discordance between gene trees and a species tree, the set of all deduced time constraints can be used to rank the species tree,i.e.order totally its internal nodes. Unfortunately lateral gene transfer detection is challenging and current methods produce a significant proportion of false positives. As a result, often, no ranking of the species tree is compatible with the full set of time constraints deduced from predicted transfers. Here we propose a method, implemented in a software called MaxTiC (Maximum Time Consistency), which takes as input a species tree and a series of (possibly inconsistent) time constraints between its internal nodes, weighted by confidence scores. MaxTiC outputs a ranked species tree compatible with a subset of constraints with maximum cumulated confidence score. We extensively test the method on simulated datasets, under a wide range of conditions that we compare to measures on biological datasets. In most conditions the obtained ranked tree is very close to the real one, confirming the potential of dating the history of life with transfers by maximizing time consistency. MaxTiC is freely available, distributed along with a documentation and several examples:https://github.com/ssolo/ALE/tree/master/maxtic.
Predicting the Evolutionary Consequences of Trophy Hunting on a Quantitative Trait
Authors: Coulson Tim , Schindler Susanne , Traill Lochran , Kendall Bruce E. 
Published: April 2017

ABSTRACTSome ecologists suggest that trophy hunting (e.g. harvesting males with a desirable trait above a certain size) can lead to rapid phenotypic change, which has led to an ongoing discussion about evolutionary consequences of trophy hunting. Claims of rapid evolution come from the statistical analyses of data, with no examination of whether these results are theoretically plausible. We constructed simple quantitative genetic models to explore how a range of hunting scenarios affects the evolution of a trophy such as horn length. We show that trophy hunting does lead to trophy evolution defined as change in the mean breeding value of the trait. However, the fastest rates of phenotypic change attributable to trophy hunting via evolution that are theoretically possible under standard assumptions of quantitative genetics are 1 to 2 orders of magnitude slower than the fastest rates reported from statistical analyses. Our work suggests a re-evaluation of the likely evolutionary consequences of trophy hunting would be appropriate when setting policy. Our work does not consider the ethical or ecological consequences of trophy hunting.
Did position-effect guide the evolutionary dynamics of developmental gene expression?
Authors: Bagadia Meenakshi , Chandradoss Keerthivasan Raanin , Jain Yachna , Singh Harpreet , Lal Mohan , Sandhu Kuljeet Singh 
Published: April 2017

AbstractConserved noncoding elements (CNEs) have significant regulatory influence on their neighbouring genes. Loss of synteny to CNEs through genomic rearrangements can, therefore, impact the transcriptional states of the cognate genes. Yet, the evolutionary implications of such chromosomal position effects have not been studied. Through genome-wide analysis of CNEs and the cognate genes of representative species from 5 different mammalian orders, we observed significant loss of synteny to CNEs in rat lineage. The CNEs and genes losing synteny had significant association with the fetal, but not the post-natal, brain development as assessed through ontology terms, developmental gene expression, chromatin marks and genetic mutations. The loss of synteny correlated with the independent evolutionary loss of fetus-specific upregulation of genes in rat brain. DNA-breakpoints implicated in brain abnormalities of germ-line origin had significant representation between CNE and the gene that exhibited loss of synteny, signifying the underlying developmental tolerance of genomic rearrangements that had allowed the evolutionary splits of CNEs and the cognate genes in rodent lineage. These observations highlighted the non-trivial impact of chromosomal position-effect in shaping the evolutionary dynamics of mammalian brain development and might explain loss of brain traits, like cerebral folding of cortex, in rodent lineage.Author SummaryExpression of genes is regulated by proximally located non-coding regulatory elements. Loss of linear proximity between gene and its regulatory element thus can alter the expression of gene. Such a phenomenon can be tested at whole genome scale using evolutionary methods. We compared the positions of genes and regulatory elements in 5 different mammals and identified the significant loss of proximities between gene and their regulatory elements in rat during evolution. Brain development related function was selectively enriched among the genes and regulatory elements that had lost the proximity in rat. The observed separation of genes and their regulatory elements was strongly associated with the evolutionary loss of developmental gene expression pattern in rat brain, which coincided with the loss of brain traits in rodents. The study highlighted the importance of relative chromosomal positioning of genes and their gene regulatory elements in the evolution of phenotypes.
A general method to fine-tune fluorophores for live-cell andin vivoimaging
Authors: Grimm Jonathan B. , Muthusamy Anand K. , Liang Yajie , Brown Timothy A. , Lemon William C. , Patel Ronak , Lu Rongwen , Macklin John J. , Keller Phillip J. , Ji Na , Lavis Luke D. 
Published: April 2017

ABSTRACTPushing the frontier of fluorescence microscopy requires the design of enhanced fluorophores with finely tuned properties. We recently discovered that incorporation of four-membered azetidine rings into classic fluorophore structures elicits substantial increases in brightness and photostability, resulting in the ‘Janelia Fluor’ (JF) series of dyes. Here, we refine and extend this strategy, showing that incorporation of 3-substituted azetidine groups allows rational tuning of the spectral and chemical properties with unprecedented precision. This strategy yields a palette of new fluorescent and fluorogenic labels with excitation ranging from blue to the far-red with utility in live cells, tissue, and animals.