bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer cells have distinct electrical properties that predict a susceptibility to lipophilic anions; a new cancer drug paradigm
Authors: Forrest Michael D. 
Published: December 2015

ABSTRACTI use the Nernst equation, parameterised with experimental data, to predict that cancer cells will accumulate more of a lipophilic anion than normal cells. This effect is correlated to charge number. Model cancer cells accumulate *100 more of an anion, *103more di-anion, *106more tri-anion, *108more tetra-anion and *1010more penta-anion (>>1 billion times more). The trend endures, conveying even greater specificity, for higher charge numbers. This effect could be leveraged for cancer therapy. Wherein the lipophilic anion is a toxin that targets some vital cellular process, which normal and cancer cells may even share. It delivers a high, lethal dose to cancer cells but a low, safe dose to normal cells. This mathematical finding conveys the prospect of a broad, powerful new front against cancer.
Recombination Disequilibrium in Ideal and Natural Populations
Authors: Tan Yuan-De 
Published: December 2015

AbstractFollowing Hardy-Weinberg disequilibrium (HWD) occurring at a single locus and linkage disequilibrium (LD) between two loci in generations, we here proposed the third genetic disequilibrium in population: recombination disequilibrium (RD). RD is a measurement of crossover interference among multiple loci in a random mating population. In natural populations besides recombination interference, RD may also be due to selection, mutation, gene conversion, drift and/or migration. Therefore, similarly to LD, RD will also reflect the history of natural selection and mutation. In breeding populations, RD purely results from recombination interference and hence can be used to build or evaluate and correct a linkage map. Several practical examples from F2, testcross and human populations indeed demonstrate that RD is useful for measuring recombination interference between two short intervals and evaluating linkage maps. As with LD, RD will be important for studying genetic mapping, association of haplotypes with disease, plant breading and population history.
A mechanistic model of linkage analysis in allohexaploids
Authors: Li Huan , Zhu Xuli , Yan Qin , Mao Ke , Wu Rongling 
Published: December 2015

AbstractDespite their pivotal role in agriculture and biological research, polyploids, a group of organisms with more than two sets of chromosomes, are very difficult to study. Increasing studies have used high-density genetic linkage maps to investigate the genome structure and function of polyploids and to identify genes underlying polyploid traits. However, although models for linkage analysis have been well established for diploids, with some essential modifications for tetraploids, no models have been available thus far for polyploids at higher ploidy levels. The linkage analysis of polyploids typically requires knowledge about their meiotic mechanisms, depending on the origin of polyplody. Here we describe a computational modeling framework for linkage analysis in allohexaploids by integrating their preferential chromosomal-pairing meiotic feature into a mixture model setting. The framework, implemented with the EM algorithm, allows the simultaneous estimates of preferential pairing factors and the recombination fraction. We investigated statistical properties of the framework through extensive computer simulation and validated its usefulness and utility by analyzing a real data from a full-sib family of allohexaploid persimmon. Our attempt in linkage analysis of allohexaploids by incorporating their meiotic mechanism lays a foundation for allohexaploid genetic mapping and also provides a new horizon to explore allohexaploid parental kinship.
High-throughput pipeline for thede novoviral genome assembly and the identification of minority variants from Next-Generation Sequencing of residual diagnostic samples
Authors: Gallo Cassarino T , Frampton D , Sugar R , Charles E , Kozlakidis Z , Kellam P 
Published: December 2015

AbstractMotivationThe underlying genomic variation of a large number of pathogenic viruses can give rise to drug resistant mutations resulting in treatment failure. Next generation sequencing (NGS) enables the identification of viral quasi-species and the quantification of minority variants in clinical samples; therefore, it can be of direct benefit by detecting drug resistant mutations and devising optimal treatment strategies for individual patients.ResultsThe ICONIC (InfeCtion respONse through vIrus genomiCs) project has developed an automated, portable and customisable high-throughput computational pipeline to assemblede novowhole viral genomes, either segmented or non-segmented, and quantify minority variants using residual diagnostic samples. The pipeline has been benchmarked on a dedicated High-Performance Computing cluster using paired-end reads from RSV and Influenza clinical samples. The median length of generated genomes was 96% for the RSV dataset and 100% for each Influenza segment. The analysis of each set lasted less than 12 hours; each sample took around 3 hours and required a maximum memory of 10 GB. The pipeline can be easily ported to a dedicated server or cluster through either an installation script or a docker image. As it enables the subtyping of viral samples and the detection of relevant drug resistance mutations within three days of sample collection, our pipeline could operate within existing clinical reporting time frames and potentially be used as a decision support tool towards more effective personalised patient treatments.AvailabilityThe software and its documentation are available fromhttps://github.com/ICONIC-UCL/pipelineContactt.cassarino@ucl.ac.uk,pk5@sanger.ac.ukSupplementary informationSupplementary data are available atBriefings in Bioinformaticsonline.
De novo identification, differential analysis and functional annotation of SNPs from RNA-seq data in non-model species
Authors: Lopez Maestre Hélène , Brinza Lilia , Marchet Camille , Kielbassa Janice , Bastien Sylvère , Boutigny Mathilde , Monnin David , El Filali Adil , Carareto Claudia Marcia , Vieira Cristina , Picard Franck , Kremer Natacha , Vavre Fabrice , Sagot Marie-France , Lacroix Vincent 
Published: December 2015

AbstractSNPs (Single Nucleotide Polymorphisms) are genetic markers whose precise identification is a prerequisite for association studies. Methods to identify them are currently well developed for model species, but rely on the availability of a (good) reference genome, and therefore cannot be applied to non-model species. They are also mostly tailored for whole genome (re-)sequencing experiments, whereas in many cases, transcriptome sequencing can be used as a cheaper alternative which already enables to identify SNPs located in transcribed regions. In this paper, we propose a method that identifies, quantifies and annotates SNPs without any reference genome, using RNA-seq data only. Individuals can be pooled prior to sequencing, if not enough material is available for sequencing from one individual. Using human RNA-seq data, we first compared the performance of our method with Gatk, a well established method that requires a reference genome. We showed that both methods predict SNPs with similar accuracy. We then validated experimentally the predictions of our method using RNA-seq data from two non-model species. The method can be used for any species to annotate SNPs and predict their impact on proteins. We further enable to test for the association of the identified SNPs with a phenotype of interest.
Rail-dbGaP: analyzing dbGaP-protected data in the cloud with Amazon Elastic MapReduce
Authors: Nellore Abhinav , Wilks Christopher , Hansen Kasper D , Leek Jeffrey T , Langmead Ben 
Published: December 2015

AbstractMotivation: Public archives contain thousands of trillions of bases of valuable sequencing data. More than 40% of the Sequence Read Archive is human data protected by provisions such as dbGaP To analyze dbGaP-protected data, researchers must typically work with IT administrators and signing officials to ensure all levels of security are implemented at their institution. This is a major obstacle, impeding reproducibility and reducing the utility of archived data.Results: We present a protocol and software tool for analyzing protected data in a commercial cloud. The protocol, Rail-dbGaP, is applicable to any tool running on Amazon Web Services Elastic MapReduce. The tool, Rail-RNA v0.2, is a spliced aligner for RNA- seq data, which we demonstrate by running on 9,662 samples from the dbGaP-protected GTEx consortium dataset. The Rail-dbGaP protocol makes explicit for the first time the steps an investigator must take to develop Elastic MapReduce pipelines that analyze dbGaP-protected data in a manner compliant with NIH guidelines. Rail-RNA automates implementation of the protocol, making it easy for typical biomedical investigators to study protected RNA-seq data, regardless of their local IT resources or expertise.Availability: Rail-RNA is available fromhttp://rail.bio. Technical details on the Rail-dbGaP protocol as well as an implementation walkthrough are available athttps://github.com/nellore/rail-dbgap. Detailed instructions on running Rail-RNA on dbGaP-protected data using Amazon Web Services are available athttp://docs.rail.bio/dbgap/.Contact:anellore@gmail.com,langmea@cs.jhu.edu
Interactive Analytics for Very Large Scale Genomic Data
Authors: Pan Cuiping , Deflaux Nicole , McInnes Gregory , Snyder Michael , Bingham Jonathan , Datta Somalee , Tsao Philip 
Published: December 2015

AbstractLarge scale genomic sequencing is now widely used to decipher questions in diverse realms such as biological function, human diseases, evolution, ecosystems, and agriculture. With the quantity and diversity these data harbor, a robust and scalable data handling and analysis solution is desired. Here we present interactive analytics using public cloud infrastructure and distributed computing database Dremel and developed according to the standards of Global Alliance for Genomics and Health, to perform information compression, comprehensive quality controls, and biological information retrieval in large volumes of genomic data. We demonstrate that such computing paradigms can provide orders of magnitude faster turnaround for common analyses, transforming long-running batch jobs submitted via a Linux shell into questions that can be asked from a web browser in seconds.
Integration of mobile sequencers in an academic classroom
Authors: Zaaijer Sophie , Erlich Yaniv ,   Columbia University Ubiquitous Genomics 2015 class
Published: December 2015

ABSTRACTThe rapid development of DNA sequencing technologies creates new educational opportunities for hands-on training. We report our experience in integrating handheld DNA sequencers (Oxford Nanopore Technologies’ MinION) as part of an academic class. This manuscript describes lessons learned to facilitate successful integration and provides educational resources for the benefit of the community.
A mechanistic first–passage time framework for bacterial cell-division timing
Authors: Ghusinga Khem Raj , Vargas-García Cesar A. , Singh Abhyudai 
Published: December 2015

AbstractHow exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells on average, add a fixed size (volume) from birth to division. Interestingly, this added volume differs considerably among genetically-identical newborn cells with similar sizes suggesting a stochastic component in the timing of cell-division. To mechanistically explain the adder principle, we consider a time-keeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that while the mean cell-division time decreases with increasing size of newborns, the noise in timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distributions of the added volume and the cell-division time when scaled by their respective means become invariant of the growth rate. Finally, we discuss various modifications to the proposed model that lead to deviations from the adder principle. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for size control.
solarius: an R interface to SOLAR for variance component analysis in pedigrees
Authors: Ziyatdinov Andrey , Brunel Helena , Martinez-Perez Angel , Buil Alfonso , Perera Alexandre , Soria Jose Manuel 
Published: December 2015

AbstractSummaryThe open source environment R is one of the most widely used software for statistical computing. It provides a variety of applications including statistical genetics. Most of the powerful tools for quantitative genetic analyses are stand-alone free programs developed by researchers in academia. SOLAR is the standard software program to perform linkage and association mappings of the quantitative trait loci (QTLs) in pedigrees of arbitrary size and complexity.solariusallows the user to exploit the variance component methods implemented in SOLAR. It automates such routine operations as formatting pedigree and phenotype data. It also parses the model output and contains summary and plotting functions for exploration of the results. In addition,solariusenables parallel computing of the linkage and association analyses, that makes the calculation of genome-wide scans more efficient.Availability and implementationsolariusis available on CRANhttps://cran.r-project.org/package=solariusand on GitHubhttps://github.com/ugcd/solarius. Seehttp://solar.txbiomedgenetics.org/for more information about SOLAR.Contactaziyatdinov@santpau.cat
Gene body H2B monoubiquitylation regulates gene-selective RNA Polymerase II pause release and is not rate limiting for transcription elongation
Authors: Fuchs Gilad , Rosenthal Eran , Bublik Debora-Rosa , Kaplan Tommy , Oren Moshe 
Published: December 2015

ABSTRACTHistone H2B monoubiquitylation (H2Bub1) is localized preferentially to transcribed regions of genes and spreads concomitantly with the progression of RNA polymerase II (Pol II). In mammalian cells, H2Bub1 levels are highly correlated with transcription elongation rates, consistent with the general belief that H2Bub1 facilitates the elongation process. Yet, a causative role of H2Bub1 in regulating elongation rates within live cells remains to be proven. Using our recently developed 4sUDRB-seq method, we examined the impact of H2Bub1 downregulation, through silencing of its cognate E3 ubiquitin ligase RNF20, on genomewide transcription elongation rates. Surprisingly, H2Bub1 downregulation had no measurable effect on global elongation rates. Instead, it led to upregulation of over 1,000 genes by altering their Pol II pause release times; notably, those genes are characterized by the presence of H2Bub1 in relatively close proximity to the paused Pol II. Conversely, another set of genes was downregulated upon partial H2Bub1 depletion, and in those genes H2Bub1 appeared to be required for efficient recruitment of Pol II to the promoter region. Overall, our data shed new light on the molecular mechanisms by which H2Bub1 regulates gene expression and imply that the role of H2Bub1 in transcription elongation should be reconsidered.AUTHOR SUMMARYTranscription elongation is an important component of the gene expression process. Numerous factors and chromatin modifications, including some that are misregulated in various human diseases, have been suggested to regulate transcription elongation. New methods to measure genomewide transcription elongation rates now enable, for the first time, to determine how a specific factor affects transcription elongation and what is the outcome of its misregulation. Using such method, we examined the role of one specific chromatin modification, histone H2B monoubiquitination (H2Bub1), in regulating transcription. Strikingly, although H2Bub1 is widely believed to serve as a regulator of transcription elongation, its downregulation did not affect genomewide elongation rates. Instead, we found that H2Bub1 regulates the expression of distinct subsets of genes by either promoting recruitment of the transcription machinery or, conversely, favoring the pausing of this machinery shortly after initiation of transcription. Our findings demonstrate that the use of genomewide elongation rate measurements can redefine the true roles of putative transcription elongation factors. Furthermore, they provide a new understanding of the functions of H2Bub1 and its impact on gene expression patterns, which is of particular interest because H2Bub1 is often downregulated in human cancer.
Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig
Authors: Edge Deirdre , Shortt Christine M , Gobbo Oliviero L , Teughels Stephanie , Prina‐Mello Adriele , Volkov Yuri , MacEneaney Peter , Radomski Marek W , Markos Farouk 
Published: December 2015

SummaryManufactured nanomaterials have a variety of medical applications, including diagnosis and targeted treatment of cancer. A series of experiments were conducted to determine the pharmacokinetic, biodistribution and biocompatibility of two novel magnetic nanoparticles (MNPs) in the anaesthetized pig. Dimercaptosuccinic acid (DMSA) coated superparamagnetic iron oxide nanoparticles (MF66‐labelled 12 nm, core nominal diameter and OD15 15 nm); at 0.5, or 2.0 mg/kg) were injected intravenously. Particles induced a dose‐dependent decrease in blood pressure following administration which recovered to control levels several minutes after injection. Blood samples were collected for a 5‐h period and stored for determination of particle concentration using particle electron paramagnetic resonance (pEPR). Organs were harvested post‐mortem for magnetic resonance imaging (MRI at 1.5 T field strength) and histology. OD15 (2.0 mg/kg) MNP had a plasma half‐life of approximately 15 min. Both doses of the MF66 (0.5 and 2.0 mg/kg) MNP were below detection limits. MNP accumulation was observed primarily in the liver and spleen with MRI scans which was confirmed by histology. MRI also showed that both MNPs were present in the lungs. The results show that further modifications may be required to improve the biocompatibility of these particles for use as diagnostic and therapeutic agents.
Serous and mucinous borderline ovarian tumours: differences in clinical presentation, high‐risk histopathological features, and lethal recurrence rates
Authors: Vasconcelos I , Darb‐Esfahani S , Sehouli J 
Published: December 2015

BackgroundMucinous and serous borderline ovarian tumours (mBOTs and sBOTs) are controversial diseases.ObjectivesWith this systematic review we aim to evaluate the different high‐risk histopathological features and recurrence rates.Search strategyThe PubMed database was searched using two terms: {serous AND [(borderline) OR (low malignant potential)] AND ovarian AND tumour} and {mucinous AND [(borderline) OR (low malignant potential)] AND ovarian AND tumour}.Selection criteriaCohorts of either sBOT or mBOT, peer‐reviewed, retrospective, or prospective.Data collection and analysisLethal recurrence data for micropapillary patterns (MPs), microinvasion, non‐invasive and invasive implants, and intraepithelial carcinoma (IECA). The primary measure of effect was the odds ratio of lethal recurrence reduction.ResultsData from patients in 42 studies including 4414 sBOTs and 12 studies including 894 mBOTs were pooled. Of these, 53.3% presented early‐stage typical sBOTs, 24.4% presented with MPs, 22.3% presented with microinvasion, 34.4% presented with non‐invasive implants, and 7.3% presented with invasive implants. The pooled lethal recurrence rates were, respectively: 18.3, 16.8, 10.7, 16.2, and 33.8%. Patients with MPs were more likely to suffer lethal recurrence when compared with high‐stage sBOTs (odds ratio, OR 0.501; P = 0.003), whereas the trend in microinvasive sBOTs did not reach statistical significance. Regarding mBOTs, 61.6% presented with early‐stage typical mBOTs, 19.6% presented with microinvasion, 34.8% presented with IECA, and six patients presented with non‐invasive implants; none presented with invasive implants. The lethal recurrence rates were, respectively: 3.6, 0, 3.7, and 0%.ConclusionMicropapillary patterns (MPs) showed a higher risk for lethal recurrence when compared with high‐stage sBOTs. Regarding mBOTs, IECA and microinvasion do not play a role in the lethal recurrence rate.Tweetable abstractMicropapillary pattern confirmed as high‐risk in BOT. IECA and microinvasion don't play a role in mucinous BOT.
Effects of chlorpyrifos on enzymatic systems of Cydia pomonella (Lepidoptera: Tortricidae) adults
Authors: Parra Morales Laura Beatriz , Alzogaray Raúl Adolfo , Cichón Liliana , Garrido Silvina , Soleño Jimena , Montagna Cristina Mónica 
Published: December 2015

AbstractThe control program of codling moth (Cydia pomonella L.) in the Río Negro and Neuquén Valley is intended to neonate larvae. However, adults may be subjected to sublethal pesticide concentrations generating stress which might enhance both mutation rates and activity of the detoxification system. This study assessed the exposure effects of chlorpyrifos on target enzyme and, both detoxifying and antioxidant systems of surviving adults from both a laboratory susceptible strain (LSS) and a field population (FP). The results showed that the FP was as susceptible to chlorpyrifos as the LSS and, both exhibited a similar chlorpyrifos‐inhibitory concentration 50 (IC50) of acetylcholinesterase (AChE). The FP displayed higher carboxylesterase (CarE) and 7‐ethoxycoumarine O‐deethylase (ECOD) activities than LSS. Both LSS and FP showed an increase on CarE activity after the exposure to low‐chlorpyrifos concentrations, followed by enzyme inhibition at higher concentrations. There were no significant differences neither in the activities of glutathione S‐transferases (GST), catalase (CAT) and superoxide dismutase (SOD) nor in the reduced glutathione (GSH) content between LSS and FP. Moreover, these enzymes were unaffected by chlorpyrifos. In conclusion, control adults from the FP exhibited higher CarE and ECOD activities than control adults from the LSS. AChE and CarE activities were the most affected by chlorpyrifos. Control strategies used for C. pomonella, such as rotations of insecticides with different modes of action, will probably delay the evolution of insecticide resistance in FPs from the study area.