bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between Facial Nerve Axonal Load and Age and Its Relevance to Facial Reanimation
Authors: Hembd Austin , Nagarkar Purushottam , Perez Justin , Gassman Andrew , Tolley Philip , Reisch Joan , White Charles L. , Rozen Shai M. 
Published: February 2017

Background:
Two-stage facial reanimation procedures with a cross-facial nerve graft often have unsatisfactory results in the older patient. Although the cause of result variability is likely multifactorial, some studies suggest that increased donor nerve axonal load improves function of a free muscle transfer after a cross-facial nerve graft. This study attempts to characterize the relationship between age and facial nerve axonal load.

Methods:
Sixty-three fresh cadaveric heads were dissected to expose the facial nerve. For each hemiface, two facial nerve samples were taken: one proximal as the nerve exits the stylomastoid foramen, and one distal at the buccal branch (at a point 1 cm proximal to the anterior parotid border). Nerve samples were stained and quantified. Correlation analysis was completed using a Pearson correlation coefficient.

Results:
Thirty-six female and 27 male cadavers were dissected; their average age was 71 years (range, 22 to 97 years). At the proximal (r = −0.26; p < 0.01; n = 104) and distal (r = −0.45; p < 0.0001; n = 114) sampling points, there was a significant negative correlation between age and axonal load.

Conclusions:
As age increases, the axonal load of the facial nerve decreases at the buccal and zygomatic branches approximately 1 cm proximal to the anterior parotid border. The authors previously suggested this location as significant for cross-facial nerve coaptation. These results propose that decreasing axonal load can be a factor in the unsatisfactory outcomes of cross-facial grafting in the aging population. Moreover, this underscores the importance of recruiting more donor axons in attempting to improve facial reanimation in the older patient.
Repli-seq: genome-wide analysis of replication timing by next-generation sequencing
Authors: Marchal Claire , Sasaki Takayo , Vera Daniel , Wilson Korey , Sima Jiao , Rivera-Mulia Juan Carlos , Trevilla García Claudia , Nogues Coralin , Nafie Ebtesam , Gilbert David M. 
Published: February 2017

ABSTRACTCycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early and late replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and sub-nuclear position. Moreover, RT is regulated during development and is altered in disease. Exploring mechanisms linking RT to other cellular processes in normal and diseased cells will be facilitated by rapid and robust methods with which to measure RT genome wide. Here, we describe a rapid, robust and relatively inexpensive protocol to analyze genome-wide RT by next-generation sequencing (NGS). This protocol yields highly reproducible results across laboratories and platforms. We also provide computational pipelines for analysis, parsing phased genomes using single nucleotide polymorphisms (SNP) for analyzing RT allelic asynchrony, and for direct comparison to Repli-chip data obtained by analyzing nascent DNA by microarrays.
microCT-Based Phenomics in the Zebrafish Skeleton Reveals Virtues of Deep Phenotyping in a Distributed Organ System
Authors: Hur Matthew , Gistelinck Charlotte A. , Huber Philippe , Lee Jane , Thompson Marjorie H. , Monstad-Rios Adrian T. , Watson Claire J. , McMenamin Sarah K. , Willaert Andy , Parichy David M , Coucke Paul , Kwon Ronald Y. 
Published: February 2017

ABSTRACTPhenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of measures comprised of morphological and densitometric traits from a large number sites in the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ. Analyzing phenotypic patterns may increase productivity in genetic screens, and could facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.
Individual nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to determine protein-RNA interactions
Authors: Sibley Christopher R. 
Published: February 2017

AbstractRNA-binding proteins (RBPs) interact with and determine the fate of many cellular RNA transcripts. In doing so they help direct many essential roles in cellular physiology, whilst their perturbed activity can contribute to disease aetiology. In this chapter we detail a functional genomics approach, termed individual nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP), that can determine the interactions of RBPs with their RNA targets in high throughput and at nucleotide resolution. iCLIP achieves this by exploiting UV-induced covalent crosslinks formed between RBPs and their target RNAs to both purify the RBP-RNA complexes under stringent conditions, and to cause reverse transcription stalling that then identifies the direct crosslink sites in the high throughput sequenced cDNA libraries.
A rareIL2RAhaplotype identifies SNP rs61839660 as causal for autoimmunity
Authors: Rainbow Daniel B. , Pekalski Marcin , Cutler Antony J. , Burren Oliver , Walker Neil , Todd John A. , Wallace Chris , Wicker Linda S. 
Published: February 2017

AbstractIL2RAis associated with multiple autoimmune diseases including type 1 diabetes (T1D). Higher expression ofIL2RAmRNA and its protein product CD25 in T lymphocytes is associated with a T1D-protective haplotype. Here we show that a rare variation of this haplotype that loses the protective allele at a single SNP, rs61839660, reducesIL2RAexpression and T1D protection, identifying it as the causal factor in disease.
Oestrogenic vascular effects are diminished by ageing
Authors: Nicholson Christopher J. , Sweeney Michèle , Robson Stephen C. , Taggart Michael J. 
Published: February 2017

AbstractThe beneficial role of oestrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance. The use of oestrogen therapy to prevent cardiovascular disease in post-menopausal women remains contentious. This study investigated the influence of the menopause and ageing on the acute vasodilatory effects of oestrogen inex vivouterine resistance arteries.Vessels were obtained from young (2.9 ± 0.1 months) and aged (24.2 ± 0.1 and 28.9 ± 0.3 months) female mice and pre-(42.3 ± 0.5 years) and post-menopausal (61.9 ± 0.9 years) women. Ageing was associated with profound structural alterations of murine uterine arteries, including the occurrence of outward hypertrophic remodelling and increased stiffness. Endothelial and smooth muscle function were diminished in uterine (and tail) arteries from aged mice and post-menopausal women. The acute vasodilatory effects of 17β-oestradiol (non-specific oestrogen receptor (ER) agonist), PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) on resistance arteries were attenuated by ageing and the menopause. However, the impairment of oestrogenic relaxation was evident after the occurrence of age-related endothelial dysfunction and diminished distensibility. The data indicate, therefore, that adverse resistance arterial ageing is a dominant factor leading to weakened vasodilatory action of oestrogenic compounds.
Modeling prediction error improves power of transcriptome-wide association studies
Authors: Bhutani Kunal , Sarkar Abhishek , Park Yongjin , Kellis Manolis , Schork Nicholas J. 
Published: February 2017

1AbstractTranscriptome-wide association studies (TWAS) test for associations between imputed gene expression levels and phenotypes in GWAS cohorts using models of transcriptional regulation learned from reference transcriptomes. However, current methods for TWAS only use point estimates of imputed expression and ignore uncertainty in the prediction. We develop a novel two-stage Bayesian regression method which incorporates uncertainty in imputed gene expression and achieves higher power to detect TWAS genes than existing TWAS methods as well as standard methods based on missing value and measurement error theory. We apply our method to GTEx whole blood transcriptomes and GWAS cohorts for seven diseases from the Wellcome Trust Case Control Consortium and find 45 TWAS genes, of which 17 do not overlap previously reported case-control GWAS or differential expression associations. Surprisingly, we replicate only 2 of 40 previously reported TWAS genes after accounting for uncertainty in the prediction.
Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial
Authors: Postma D.F. , Spitoni C. , van Werkhoven C.H. , van Elden L.J.R. , Oosterheert J.J. , Bonten M.J.M. 
Published: February 2017

ABSTRACTBackgroundGuidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events.ObjectiveTo quantify associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards.DesignPost-hoc analysis of a cluster-randomized trialSettingSix hospitals in the NetherlandsPatientsCAP patients admitted to non-ICU wards and without a cardiac event on admissionMeasurementsCause-specific hazard ratio’s (HR’s) were calculated for effects of time-dependent macrolide and fluoroquinolone exposure on cardiac events, defined as occurrence of new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization.ResultsCardiac events occurred in 146 (6.9%) of 2,107 patients and included episodes of heart failure (n=101, 4.8%), arrhythmia (n=53, 2.5%), and myocardial ischemia (n=14, 0.7%). Cardiac events occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, respectively, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) patients exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Hazard ratios for any cardiac event, adjusted for confounding, were 0.89 (95% confidence interval (CI) 0.48 to 1.67), 1.06 (95% CI 0.61 to 1.83) and 1.68 (95% CI 1.07 to 2.62) for azithromycin, clarithromycin, and erythromycin, respectively, and adjusted hazard ratios were 0.86 (95% CI 0.47 to 1.57), 0.42 (95% CI 0.18 to 0.96) and 0.62 (95% CI 0.39 to 0.99) for ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Erythromycin was associated with an adjusted hazard ratio of 2.08 (95% CI 1.25 to 3.46) for heart failure.LimitationsPossibility of confounding by indication and observational biasConclusionsAmong patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure.RegistrationThe original trial was registered under ClinicalTrials.gov IdentifierNCT01660204Funding SourceThe Netherlands Organization for Health Research and Development (ZONmw, Health care efficiency research, project id: 171202002).
Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice
Authors: Mikumo Hironori , Yanagihara Toyoshi , Hamada Naoki , Harada Eiji , Ogata-Suetsugu Saiko , Ikeda-Harada Chika , Arimura-Omori Masako , Suziki Kunihiro , Yokoyama Tetsuya , Nakanishi Yoichi 
Published: February 2017

ABSTRACTBackground and objectiveGefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice.MethodsC57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/kg) was orally administered to mice from day −1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14.ResultsSivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. Conclusions: These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.Summary statementNeutrophil elastase inhibitor sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.
The regulation of tDNA transcription during the directed differentiation of stem cells
Authors: Woolnough J. L , Schneider D. A. , Giles K.E. 
Published: February 2017

AbstractThe human genome consists of 625 tDNA copies that encode 51 distinct isoacceptor families. Recent studies demonstrated that changes in chromatin structure during cellular differentiation can alter the expression of these tDNA. However, the mechanism by which tDNA can be differentially regulated remains unclear. Here we used the directed differentiation of pluripotent human embryonic stem cells (hESCs) towards the endoderm lineage as a model system to study the developmental regulation of individual tDNA. We demonstrated a significant change in the Pol III occupancy at 49 tDNA (22 reduced and 27 increased). The regulation of tDNA did not correlate with changes in TFIIIB or TFIIIC occupancy, H3K4me3, or H3K27me3 levels. However, tDNA that had an increase in Pol III binding were preferentially found within strong CTCF-COHESIN chromatin loops. The knockdown of either Ctcf or Rad21 in mouse tail tip fibroblasts had similar effects on changes in tRNA levels. We identified 7 isoacceptors that were differentially expressed during the directed differentiation of hESCs. The open reading frames of the ribosomal protein genes, which are translationally repressed during hESC differentiation, are enriched for codons that are decoded by these downregulated isoacceptors. Thus, translation efficiency during cellular differentiation may be affected by changes in tDNA regulation.
A generator of morphological clones for plant species
Authors: Potapov Ilya , Järvenpää Marko , Åkerblom Markku , Raumonen Pasi , Kaasalainen Mikko 
Published: February 2017

AbstractDetailed and realistic tree form generators have numerous applications in ecology and forestry. Here, we present an algorithm for generating morphological tree “clones” based on the detailed reconstruction of the laser scanning data, statistical measure of similarity, and a plant growth algorithm with simple stochastic rules. The algorithm is designed to produce tree forms, i.e. morphological clones, similar as a whole (coarse-grain scale), but varying in minute details of organization (fine-grain scale). We present a general procedure for obtaining these morphological clones. Although we opted for certain choices in our algorithm, its various parts may vary depending on the application. Namely, we have shown that specific multi-purpose procedural stochastic growth model can be algorithmically adjusted to produce the morphological clones replicated from the target experimentally measured tree. For this, we have developed a statistical measure of similarity (structural distance) between any given pair of trees, which allows for the comprehensive comparing of the tree morphologies in question by means of empirical distributions describing geometrical and topological features of a tree. Our algorithm can be used in variety of applications and contexts for exploration of the morphological potential of the growth models, arising in all sectors of plant science research.Summary StatementWe present an algorithmic framework, based on the Bayesian inference, for generating morphological tree clones using a combination of stochastic growth models and experimentally derived tree structures.
Unmet Needs for Analyzing Biological Big Data: A Survey of 704 NSF Principal Investigators
Authors: Barone Lindsay , Williams Jason , Micklos David 
Published: February 2017

AbstractIn a 2016 survey of 704 National Science Foundation (NSF) Biological Sciences Directorate principal investigators (BIO PIs), nearly 90% indicated they are currently or will soon be analyzing large data sets. BIO PIs considered a range of computational needs important to their work—including high performance computing (HPC), bioinformatics support, multi-step workflows, updated analysis software, and the ability to store, share, and publish data. Previous studies in the United States and Canada emphasized infrastructure needs. However, BIO PIs said the most pressing unmet needs are training in data integration, data management, and scaling analyses for HPC—acknowledging that data science skills will be required to build a deeper understanding of life. This portends a growing data knowledge gap in biology and challenges institutions and funding agencies to redouble their support for computational training in biology.
mixOmics: an R package for ‘omics feature selection and multiple data integration
Authors: Rohart Florian , Gautier Benoît , Singh Amrit , Lê Cao Kim-Anh 
Published: February 2017

AbstractThe advent of high throughput technologies has led to a wealth of publicly available ‘omics data coming from different sources, such as transcriptomics, proteomics, metabolomics. Combining such large-scale biological data sets can lead to the discovery of important biological insights, provided that relevant information can be extracted in a holistic manner. Current statistical approaches have been focusing on identifying small subsets of molecules (a ‘molecular signature’) to explain or predict biological conditions, but mainly for a single type of ‘omics. In addition, commonly used methods are univariate and consider each biological feature independently.We introducemixOmics, an R package dedicated to the multivariate analysis of biological data sets with a specific focus on data exploration, dimension reduction and visualisation. By adopting a system biology approach, the toolkit provides a wide range of methods that statistically integrate several data sets at once to probe relationships between heterogeneous ‘omics data sets. Our recent methods extend Projection to Latent Structure (PLS) models for discriminant analysis, for data integration across multiple ‘omics data or across independent studies, and for the identification of molecular signatures. We illustrate our latestmixOmicsintegrative frameworks for the multivariate analyses of ‘omics data available from the package.
Evaluation of anticancer and anti-mitotic properties of quinazoline and quinazolino-benzothiadiazine derivatives
Authors: Shaik Thoukhir B. , Malik M. Shaheer , Seddigid Zaki S. , Routhu Sunitha R , Kamal Ahmed 
Published: February 2017

AbstractCancer is one of the major health and social-economic problems despite considerable progress in its early diagnosis and treatment. Owing to the emergence and increase of multi drug resistance to various conventional drugs, and the continuing importance on health-care expenditure, many researchers have focused to develop novel and effective anticancer compounds. In the present study, a series of in-house synthesized quinazoline and quinazolino-benzothiadiazine derivatives were investigated for their anticancer efficacy against a panel of five cancer (DU145, MCF7, HepG2, SKOV3 and MDA-MB-231) and one normal (MRC5) cell lines. Among all the tested compounds, fifteen of them exhibited promising growth-inhibitory effect (0.15 - 5.0 μM) and induced cell cycle arrest in G2/M phase. In addition, the selected compounds inhibited the microtubule assembly; altered mitochondrial membrane potential and enhanced the levels of caspase-9 in MCF-7 cells. Furthermore, the active compound with combination of drugs showed synergistic effect at lower concentrations and the drug uptake was mediated through clathrin mediated endocytic pathway. Our results indicated that quinazoline and quinazolino-benzothiadiazine conjugates could serve as potential leads in the development of personalized cancer therapeutics.SummaryThe present study describes the exploration of small molecules based on heterocyclic scaffolds for tubulin target based development of anticancer agents.
Inferring demographic history using two-locus statistics
Authors: Ragsdale Aaron P. , Gutenkunst Ryan N. 
Published: February 2017

AbstractPopulation demographic history may be learned from contemporary genetic variation data. Methods based on aggregating the statistics of many single loci into an allele frequency spectrum (AFS) have proven powerful, but such methods ignore potentially informative patterns of linkage disequilibrium (LD) between neighboring loci. To leverage such patterns, we developed a composite-likelihood framework for inferring demographic history from aggregated statistics of pairs of loci. Using this framework, we show that two-locus statistics are indeed more sensitive to demographic history than single-locus statistics such as the AFS. In particular, two-locus statistics escape the notorious confounding of depth and duration of a bottleneck, and they provide a means to estimate effective population size based on the recombination rather than mutation rate. We applied our approach to a Zambian population ofDrosophila melanogaster. Notably, using both single– and two-locus statistics, we found substantially lower estimates of effective population size than previous works. Together, our results demonstrate the broad potential for two-locus statistics to enable powerful population genetic inference.