bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mitochondrial DNA Control Region might have useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors
Authors: Bircan Rifat , Gözü Hülya Iliksu , Esra Ulu , Sarikaya Şükran , Gül Aylin Ege , Yaşar Şirin Duygu , Özçelik Serhat , Aral Cenk 
Published: March 2018

AbstractBackgroundIt is currently present in the literature that mitochondrial DNA (mtDNA) defects are associated with a great number of diseases including cancers. The role of mitochondrial DNA (mtDNA) variations in the development of thyroid cancer is a highly controversial topic. In this study, we investigated the role of mt-DNA control region (CR) variations in thyroid tumor progression and the influence of mtDNA haplogroups on susceptibility to thyroid tumors.Material & methodFor this purpose, totally 108 hot thyroid nodules (HTNs), 95 cold thyroid nodules (CTNs), 48 papillary thyroid carcinoma (PTC) samples with their surrounding tissues and 104 healthy control subject’s blood samples were screened for entire mtDNA CR variations by using Sanger sequencing. The obtained DNA sequences were anaysed with the mistomaster, a web-based bioinformatics tool.ResultsMtDNA haplogroup U was significantly associated with susceptibility to benign and malign thyroid entities on the other hand J haplogroup was associated with a protective role for benign thyroid nodules. Besides, 8 SNPs (T146C, G185A, C194T, C295T, G16129A, T16304C, A16343G and T16362C) in mtDNA CR region were associated with the occurrence of benign and malign thyroid nodules in Turkish population. By contrast with the healthy Turkish population and HTNs, frequency of C7 repeats in D310 polycytosine sequence was found higher in cold thyroid nodules and PTC samples. Beside this, the frequency of somatic mutations in mtMSI regions including T16189C and D514 CA dinucleotide repeats were found higher in PTC samples than the benign thyroid nodules. Conversely, the frequency of somatic mutations in D310 was detected higher in HTNs than CTNs and PTCs.ConclusionmtDNA D310 instability do not play a role in tumorogenesis of the PTC but the results indicates that it might be used as a diagnostic clonal expansion biomarker for premalignant thyroid tumor cells. Beside this, D514 CA instability might be used as prognostic biomarker in PTCs. Also, we showed that somatic mutation rate is less frequent in more aggressive tumors when we examined micro- and macro carcinomas as well as BRAFV600E mutation.
Adult influence on juvenile phenotypes by stage-specific pheromone production
Authors: Werner Michael S. , Claaßen Marc H. , Renahan Tess , Dardiry Mohannad , Sommer Ralf. J. 
Published: March 2018

SummaryMany animal and plant species respond to high or low population densities by phenotypic plasticity. To investigate if specific age classes and/or cross-generational signaling affect(s) phenotypic plasticity, we developed a dye-based method to differentiate co-occurring nematode age classes. We applied this method toPristionchus pacificus, which develops a predatory mouth form to exploit alternative resources and kill competitors in response to high population densities. Remarkably, only adult, but not juvenile, crowding induces the predatory morph in other juveniles. Profiling of secreted metabolites throughout development with HPLC-MS combined with genetic mutants traced this result to the production of adult-specific pheromones. Specifically, theP. pacificus-specific di-ascaroside#1 that induces the predatory morph exhibits a binary induction in adults, even though mouth form is no longer plastic in adults. This cross-generational signaling between adults and juveniles may serve as an indication of rapidly increasing population size. Thus, phenotypic plasticity depends on critical age classes.
Design and evaluation of a large sequence-capture probe set and associated SNPs for diploid and haploid samples of Norway spruce (Picea abies)
Authors: Vidalis Amaryllis , Scofield Douglas G. , Neves Leandro G. , Bernhardsson Carolina , García-Gil María Rosario , Ingvarsson Pär K. 
Published: March 2018

AbstractMassively parallel sequencing has revolutionized the field of genetics by providing comparatively high-resolution insights into whole genomes for large number of species so far. However, whole-genome resequencing of many conspecific individuals remains cost-prohibitive for most species. This is especially true for species with very large genomes with extensive genomic redundancy, such as the genomes of coniferous trees. The genome assembly for the conifer Norway spruce (Picea abies) was the first published draft genome assembly for any gymnosperm. Our goal was to develop a dense set of genome-wide SNP markers for Norway spruce to be used for assembly improvement and population studies. From 80,000 initial probe candidates, we developed two partially-overlapping sets of sequence capture probes: one developed against 56 haploid megagametophytes, to aid assembly improvement; and the other developed against 6 diploid needle samples, to aid population studies. We focused probe development within genes, as delineated via the annotation of ~67,000 gene models accompanying P. abies assembly version 1.0. The 31,277 probes developed against megagametophytes covered 19,268 gene models (mean 1.62 probes/model). The 40,018 probes developed against diploid tissue covered 26,219 gene modules (mean 1.53 probes/model). Analysis of read coverage and variant quality around probe sites showed that initial alignment of captured reads should be done against the whole genome sequence, rather than a subset of probe-containing scaffolds, to overcome occasional capture of sequences outside of designed regions. All three probe sets, anchored to the P. abies 1.0 genome assembly and annotation, are available for download.
Genomic normalization for sequencing libraries enrichment for rare somatic retroelement insertions
Authors: Komkov Alexander , Nugmanov Gaiaz , Salutina Maria , Minervina Anastasia , Khodosevich Konstantin , Lebedev Yuri , Mamedov Ilgar 
Published: March 2018

AbstractBackgroundThere is increasing evidence that the transpositional activity of retroelements (REs) is not limited to germ line cells, but often occurs in tumor and normal somatic cells. Somatic transpositions were found in several human tissues and are especially typical for the brain. Several computational and experimental approaches for detection of somatic retroelement insertions was developed in the past few years. These approaches were successfully applied to detect somatic insertions in clonally expanded tumor cells. At the same time, identification of somatic insertions presented in small proportion of cells, such as neurons, remains a considerable challenge.ResultsIn this study, we developed a normalization procedure for library enrichment by DNA sequences corresponding to rare somatic RE insertions. Two rounds of normalization increased the number of fragments adjacent to somatic REs in the sequenced sample by more than 26-fold, and the number of identified somatic REs was increased by 7.9-fold.ConclusionsThe developed technique can be used in combination with vast majority of modern RE identification approaches and can dramatically increase their capacity to detect rare somatic RE insertions in different types of cells.
AutonoMouse: High throughput automated operant conditioning shows progressive behavioural impairment with graded olfactory bulb lesions
Authors: Erskine Andrew , Bus Thorsten , Herb Jan T. , Schaefer Andreas T. 
Published: March 2018

AbstractOperant conditioning is a crucial tool in neuroscience research for probing brain function. While molecular, anatomical and even physiological techniques have seen radical increases in throughput, efficiency, and reproducibility in recent years, behavioural tools have seen much less of an improvement. Here we present a fully automated, high-throughput system for self-initiated conditioning of up to 25 group-housed, radio-frequency identification (RFID) tagged mice over periods of several months and >10^6 trials. We validate this “AutonoMouse” system in a series of olfactory behavioural tasks and show that acquired data is comparable to previous semi-manual approaches. Furthermore, we use AutonoMouse to systematically probe the impact of graded olfactory bulb lesions on olfactory behaviour and resolve the long-standing conundrum about the apparent lack of impact of lesions on olfactory abilities. The modular nature and open-source design of AutonoMouse should allow for similar robust and systematic assessments across neuroscience research areas.
Dorsal Hippocampal Activation Suppresses Neuropathic Pain Behaviors: Chronic pain as extinction-resistant pain-related memory traces
Authors: Xuhong Wei , Ren W. , Centeno M.V. , Procissi D. , Xu Ting , Jabakhanji R. , Martina M. , Radulovic J. , Surmeier D. J. , Liu X.G. , Apkarian A.V. 
Published: March 2018

AbstractAccumulating evidence suggests the hippocampus being involved in, and modified with, chronic neuropathic pain. However, it is still not clear whether hippocampal activity has direct control over neuropathic behaviors. Here we show that activation of the dorsal, but not ventral, hippocampus, by glutamate microinjection or by chemogenetically increasing excitability (PSAM/PSEM), completely or partially reversed neuropathic behaviors: tactile allodynia and thermal hyperalgesia in the models of spared nerve injury and lumbar spinal nerve ligation. Using a new methodology (chemo-fMRI), where we combine awake resting state brain imaging with viral vector mediated chemogenetic activation (PSAM/PSEM), we could demonstrate that increased excitability of dorsal hippocampus neurons altered resting state functional connectivity within circuitry specifically related to the extent of diminution of neuropathic behavior (tactile allodynia). The identified circuitry most reliably (survived a validation procedure) identified dorsal hippocampal connections to the somatosensory cortex and the thalamus. Moreover, anterograde tracing indicated non-overlapping projections from dorsal and ventral hippocampus. Thus, the present study exhibits a novel causal role for the dorsal hippocampus, and mediating circuitry, controlling neuropathic pain-related behaviors. Altogether, these results imply downregulation of dorsal hippocampus circuitry in chronic neuropathic pain; the activation of which reverses pain behaviors either through disruption of accumulated memories and/or by enhancing extinction circuitry.
Characterisation of palytoxin from an undescribed Palythoa (Anthozoa: Zoantharia: Sphenopidae) with significant in vitro cytotoxic effects on cancer cells at picomolar doses
Authors: Sawelew Ludovic , Gault Frédéric , Nuccio Christopher , Perez Yvan , Lorquin Jean 
Published: March 2018

AbstractPalytoxin (PlTX), a large polyhydroxylated compound, is among the most potent non-peptide toxin in marine organisms known so far. The literature emphasizes the sodium/potassium pump (NaK) as the privileged target for PlTX when exerting its toxic effects. In this study, we focused on an undescribed species (Palythoa sp. Pc001), a coral species belonging to the genus Palythoa routinely cultivated in aquariums. We demonstrated that this species contains one of the highest yields of pure PlTX production ever found, 2.22 ± 0.41 mg PlTX per gram of wet Palythoa. Using molecular data combined with external morphology, we identified Palythoa sp. Pc001 as the sister species to Palythoa aff. clavata. Further, the clade of a symbiotic Symbiodinium sp. was characterised by DNA barcoding and pigment content. Molecular data showed that Palythoa sp. Pc001 contains ‘generalist’ Symbiodinium belonging to clade C. This paper also describes for the first time the localisation of PlTX and Symbiodinium cells in tissues of a highly toxic Palythoa species. PlTX toxicity was assayed on 72 h-cultured murine and human cancer cells versus the normal human dermal fibroblast (NHDF; PC C12300) cell line. Using MTT colorimetric assay and quantitative videomicroscopy, our results showed much higher in vitro cytotoxic activity on cancer cells (IC50 0.54 ± 0.05 × 10−12 M) than on non-cancerous ones (IC50 > 1 × 10−6 M). Such a strong differential effect has never been reported with respect to the most potent NaK ligands (cardiac glycosides) described so far. Moreover, PlTX displayed similar in vitro growth inhibitory activity in rodent and human cancer cells, although the NaK in rodents displays a double mutation in the α1-subunit that usually decreases the sensitivity to others cardiac glycosides like ouabain, when compared to human cells. This work demonstrates, first, that picomolar concentrations of PlTX have significant higher cytotoxic effects on cancer cells than on non-cancerous ones, and secondly, that this in vitro antitumor effect would not be entirely relied onto its canonical targeting to the NaK α-subunit. Thus, PlTX ranks amongst highly potent anti-cancer drugs as it targets cancers while potentially minimizing the drug’s side effects on healthy cells.
Sensitivity Levels: Optimizing the Performance of Privacy Preserving DNA Alignment
Authors: Fernandes Maria , Decouchant Jérémie , Völp Marcus , Couto Francisco M , Esteves-Veríssimo Paulo 
Published: March 2018

AbstractThe advent of high throughput next-generation sequencing (NGS) machines made DNA sequencing cheaper, but also put pressure on the genomic life-cycle, which includes aligning millions of short DNA sequences, called reads, to a reference genome. On the performance side, efficient algorithms have been developed, and parallelized on public clouds. On the privacy side, since genomic data are utterly sensitive, several cryptographic mechanisms have been proposed to align reads securely, with a lower performance than the former, which in turn are not secure. This manuscript proposes a novel contribution to improving the privacy performance product in current genomic studies. Building on recent works that argue that genomics data needs to be × treated according to a threat-risk analysis, we introduce a multi-level sensitivity classification of genomic variations. Our classification prevents the amplification of possible privacy attacks, thanks to promoting and partitioning mechanisms among sensitivity levels. Thanks to this classification, reads can be aligned, stored, and later accessed, using different security levels. We then extend a recent filter, which detects the reads that carry sensitive information, to classify reads into sensitivity levels. Finally, based on a review of the existing alignment methods, we show that adapting alignment algorithms to reads sensitivity allows high performance gains, whilst enforcing high privacy levels. Our results indicate that using sensitivity levels is feasible to optimize the performance of privacy preserving alignment, if one combines the advantages of private and public clouds.
Nonlinear calcium ion waves along actin filaments control active hair–bundle motility
Authors: A.Tuszynski J. , Sataric M. V. , Sekulic D. L. , Sataric B. M. , Zdravkovic S. 
Published: March 2018

AbstractActin filaments are highly dynamic semiflexible cellular biopolymers with diverse functions, such as cell motility. They also play the role of conduits for propagation of calcium ion waves. In this paper, we propose a new biophysical model that describes how actin filaments with their polyelectrolyte properties serve as pathways for calcium ion flows in hair cells. We show this can be utilized for the tuning of force–generating myosin motors. In this model, we unify the calcium nonlinear dynamics involved in the control of the myosin adaptation motors with mechanical displacements of hair– bundles. The model shows that the characteristic time scales fit reasonably well with the available experimental data for spontaneous oscillations in the inner ear. This model offers promises to fill a gap in our understanding of the role of calcium ion nonlinear dynamics in the regulation of processes in the auditory cells of the inner ear.
A post-transcriptional regulatory code for mRNA stability during the zebrafish maternal-to-zygotic transition
Authors: Vejnar Charles E. , Messih Mario Abdel , Takacs Carter M. , Yartseva Valeria , Oikonomou Panos , Christiano Romain , Stoeckius Marlon , Lau Stephanie , Lee Miler T. , Beaudoin Jean-Denis , Darwich-Codore Hiba , Walther Tobias C. , Tavazoie Saeed , fuentes Daniel Ci- , Giraldez Antonio J. 
Published: March 2018

AbstractPost-transcriptional regulation is crucial to shape gene expression. During the Maternal-to-Zygotic Transition (MZT), thousands of maternal transcripts are regulated upon fertilization and genome activation. Transcript stability can be influenced bycis-elements andtrans-factors, but how these inputs are integrated to determine the overall mRNA stability is unclear. Here, we show that most transcripts are under combinatorial regulation by multiple decay pathways during zebrafish MZT. To identifycis-regulatory elements, we performed a massively parallel reporter assay for stability-influencing sequences, which revealed that 3’-UTR poly-U motifs are associated with mRNA stability. In contrast, miR-430 target sequences, UAUUUAUU AU-rich elements (ARE), CCUC and CUGC elements emerged as the main destabilizing motifs in the embryo, with miR-430 and AREs causing mRNA deadenylation in a genome activation-dependent manner. To identify thetrans-factors interacting with thesecis-elements, we comprehensively profiled RNA-protein interactions and their associated regulatory activities across the transcriptome during the MZT. We find that poly-U binding proteins are preferentially associated with 3’-UTR sequences and stabilizing motifs, and that antagonistic sequence contexts for poly-C and poly-U binding proteins shape the binding landscape and magnitude of regulation across the transcriptome. Finally, we integrate these regulatory motifs into a machine learning model that accurately predicts the stability of mRNA reportersin vivo. Our findings reveal how mechanisms of post-transcriptional regulation are coordinated to direct changes in mRNA stability within the early zebrafish embryo.
Disclosure of pension asset allocation and expected rate of return management
Authors: Hwang Seokyoun , Sarath Bharat 
Published: March 2018

Purpose
The purpose of this paper is to examine whether the expected rate of return (ERR) management is related to disclosure of pension asset allocation. FAS 132R(1), which requires firms to disaggregate the detailed categories of pension asset allocation, provides a natural experiment setting for investigating the effect of enhanced transparency on firm behavior.

Design/methodology/approach
The authors focus on the variation of voluntary disclosure and its effect on ERR management under the two different reporting regimes. The authors measure the variation of voluntary disclosure of the pension asset allocations in the pre-period of FAS 132R(1), by using the self-constructed disclosure score.

Findings
First, firms create flexibility in their choice of ERR through opaque disclosure of pension asset allocation. Next, firms with poor disclosures are more likely to adjust ERR downward when accounting standards require greater transparency, implying that, for firms with poor disclosures, mandated transparency in pension asset allocation plays a vital role in reducing the ERR management.

Research limitations/implications
The authors directly illustrate the impact of FAS 132R(1) on ERR management. The authors find that the impact of mandated transparency is not uniform across firms. Next, this study highlights the importance of disclosure in restricting managers’ earnings management motivation.

Originality/value
The authors hand collect the asset allocations under pre-FAS 132R(1) period from the 10-K pension footnotes for all S&P 500 firms, which allows the authors to identify the disclosure variation amongst the firms. Based on the variation of disclosure, the authors construct the ordinal measure of disclosure scores on which the testing indicator variables are built.
Abusive supervision and job-oriented constructive deviance in the hotel industry
Authors: Pan Wen , Sun Liuyuan , Sun Li-yun , Li Chenwei , Leung Alicia S.M. 
Published: March 2018

PurposeDrawing on activation theory, this paper aims to examine the process through which abusive supervision influences job-oriented constructive deviance (JCD) in the hospitality industry.Design/methodology/approachData are collected from 198 employees working with 34 supervisors, at three time points across four hotel groups in Macau. The instantaneous indirect effect and moderated curvilinear effect using established measures are tested.FindingsFirst, abusive supervision was positively associated with hotel employees’ job dissatisfaction and their job dissatisfaction had an inverted curvilinear effect on JCD. Second, job dissatisfaction nonlinearly mediated the impact of abusive supervision on JCD. Third, high problem-focused coping decelerated the diminishing benefits of job dissatisfaction on JCD.Practical implicationsFirst, organizations should accept employees’ constructive deviance but suppress managers’ abusive supervision. Second, organizations need to improve employees’ problem-focused coping skills and channel job dissatisfaction into constructive and active behaviors.Originality/valueTheoretically, the authors test a nonlinearly mediating and moderated curvilinear model and address the research concern on whether, why and how service employees decide to engage in positive deviant behaviors when encountering abusive supervision. Practically, the authors avoid concluding that moderate levels of abusive supervision can promote positive employee behaviors and refrain from justification of abusive supervision in the hospitality context.
Directional‐oriented wavefield imaging: a new wave‐based subsurface illumination imaging condition for reverse time migration
Authors: Kim Young Seo , Tsingas Constantine , Jeong Woodon 
Published: March 2018

ABSTRACTThe key objective of an imaging algorithm is to produce accurate and high‐resolution images of the subsurface geology. However, significant wavefield distortions occur due to wave propagation through complex structures and irregular acquisition geometries causing uneven wavefield illumination at the target. Therefore, conventional imaging conditions are unable to correctly compensate for variable illumination effects. We propose a generalised wave‐based imaging condition, which incorporates a weighting function based on energy illumination at each subsurface reflection and azimuth angles. Our proposed imaging kernel, named as the directional‐oriented wavefield imaging, compensates for illumination effects produced by possible surface obstructions during acquisition, sparse geometries employed in the field, and complex velocity models. An integral part of the directional‐oriented wavefield imaging condition is a methodology for applying down‐going/up‐going wavefield decomposition to both source and receiver extrapolated wavefields. This type of wavefield decomposition eliminates low‐frequency artefacts and scattering noise caused by the two‐way wave equation and can facilitate the robust estimation for energy fluxes of wavefields required for the seismic illumination analysis. Then, based on the estimation of the respective wavefield propagation vectors and associated directions, we evaluate the illumination energy for each subsurface location as a function of image depth point and subsurface azimuth and reflection angles. Thus, the final directional‐oriented wavefield imaging kernel is a cross‐correlation of the decomposed source and receiver wavefields weighted by the illuminated energy estimated at each depth location. The application of the directional‐oriented wavefield imaging condition can be employed during the generation of both depth‐stacked images and azimuth–reflection angle‐domain common image gathers. Numerical examples using synthetic and real data demonstrate that the new imaging condition can properly image complex wave paths and produce high‐fidelity depth sections.