bluuebunny/crossref_metadata_2025_split huggingface dataset:
The TRIM-NHL protein NHL-2 is a Novel Co-Factor of the CSR-1 and HRDE-1 22G-RNA Pathways
Authors: Davis Gregory M. , Tu Shikui , Colson Rhys N. , Anderson Joshua W. T. , Gunzburg Menachem J. , Francisco Michelle A. , Ray Debashish , Maity Tuhin , Wu Monica Z. , Morris Quaid D. , Hughes Timothy R. , Wilce Jacqueline A. , Claycomb Julie M. , Weng Zhiping , Boag Peter R. 
Published: February 2018

ABSTRACTProper regulation of germline gene expression is essential for fertility and maintaining species integrity. In theC. elegansgermline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in theC. elegansgermline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.
Beyond the vestibulo-ocular reflex: Vestibular input is processed centrally to achieve visual stability
Authors: Dalmaijer Edwin S. 
Published: February 2018

AbstractThe current study presents a re-analysis of data from Zink et al. (1998, Electroencephalography and Clinical Neurophysiology, 107), who administered galvanic vestibular stimulation through unipolar direct current. They placed electrodes on each mastoid, and applied both right and left anodal stimulation. Ocular torsion and visual tilt were measured under different stimulation intensities. New modelling introduced here demonstrates that directly proportional linear models fit reasonably well to the relationship between vestibular input and visual tilt, but not to that between vestibular input and ocular torsion. Instead, an exponential model characterised by a decreasing slope and an asymptote fitted best. These results demonstrate that in the results presented by Zink et al., ocular torsion could not completely account for visual tilt. This suggests that vestibular input is processed centrally to stabilise vision when ocular torsion is insufficient. Potential mechanisms and seemingly conflicting literature are discussed.
Interconnected feedback loops among ESRP1, HAS2, and CD44 regulate epithelial-mesenchymal plasticity in cancer
Authors: Jolly Mohit Kumar , Preca Bogdan-Tiberius , Tripathi Satyendra C , jia Dongya , Hanash Samir M , Brabletz Thomas , Stemmler Marc P , Maurer Jochen , Levine Herbert 
Published: February 2018

AbstractAberrant activation of epithelial-mesenchymal transition (EMT) in carcinoma cells contributes to increased migration and invasion, metastasis, drug resistance, and tumor-initiating capacity. EMT is not always a binary process, rather cells may exhibit a hybrid epithelial/mesenchymal (E/M) phenotype. ZEB1 - a key transcription factor driving EMT - can both induce and maintain a mesenchymal phenotype. Recent studies have identified two novel autocrine feedback loops utilizing ESRP1, HAS2, and CD44 that maintain high levels of ZEB1. However, how the crosstalk between these feedback loops alters the dynamics of epithelial-hybrid-mesenchymal transition remains elusive. Here, using an integrated theoretical-experimental framework, we identify that these feedback loops can enable cells to stably maintain a hybrid E/M phenotype. Moreover, computational analysis identifies the regulation of ESRP1 as a crucial node, a prediction that is validated by two complementary experiments showing that (a) overexpression of ESRP1 reverts EMT in MCF10A cells treated with TGFβ for 21 days, and (b) knockdown of ESRP1 in stable hybrid E/M H1975 cells drives EMT. Finally, in multiple breast cancer datasets, high levels of ESRP1, ESRP1/HAS2, and ESRP1/ZEB1 correlates with poor prognosis, supporting the relevance of ZEB1/ESRP1 and ZEB1/HAS2 axes in tumor progression. Together, our results unravel how these interconnected feedback loops act in concert to regulate ZEB1 levels and to drive the dynamics of epithelial-hybrid-mesenchymal transition.
ASGAL: Aligning RNA-Seq Data to a Splicing Graph to Detect Novel Alternative Splicing Events
Authors: Denti Luca , Rizzi Raffaella , Beretta Stefano , Della Vedova Gianluca , Previtali Marco , Bonizzoni Paola 
Published: February 2018

AbstractBackground: While the reconstruction of transcripts from a sample of RNA-Seq data is a computationally expensive and complicated task, the detection of splicing events from RNA-Seq data and a gene annotation is computationally feasible. The latter task, which is adequate for many transcriptome analyses, is usually achieved by aligning the reads to a reference genome, followed by comparing the alignments with a gene annotation, often implicitly represented by a graph: the splicing graph.Results: We present ASGAL (Alternative Splicing Graph ALigner): a tool for mapping RNA-Seq data to the splicing graph, with the main goal of detecting novel alternative splicing events. ASGAL receives in input the annotated transcripts of a gene and an RNA-Seq sample, and it computes (1) the spliced alignments of each read, and (2) a list of novel events with respect to the gene annotation.Conclusions: An experimental analysis shows that, by aligning reads directly to the splicing graph, ASGAL better predicts alternative splicing events when compared to tools requiring spliced alignments of the RNA-Seq data to a reference genome. To the best of our knowledge, ASGAL is the first tool that detects novel alternative splicing events by directly aligning reads to a splicing graph.Availability: Source code, documentation, and data are available for download at http://asgal.algolab.eu.
Chromosome-scale comparative sequence analysis unravels molecular mechanisms of genome evolution between two wheat cultivars
Authors: Thind Anupriya Kaur , Wicker Thomas , Müller Thomas , Ackermann Patrick M. , Steuernagel Burkhard , Wulff Brande B.H. , Spannagl Manuel , Twardziok Sven O. , Felder Marius , Lux Thomas , Mayer Klaus F.X. ,   International Wheat Genome Sequencing Consortium, Keller Beat , Krattinger Simon G. 
Published: February 2018

AbstractBackgroundRecent improvements in DNA sequencing and genome scaffolding have paved the way to generate high-qualityde novoassemblies of pseudomolecules representing complete chromosomes of wheat and its wild relatives. These assemblies form the basis to compare the evolutionary dynamics of wheat genomes on a megabase-scale.ResultsHere, we provide a comparative sequence analysis of the ~700-megabase chromosome 2D between two bread wheat genotypes – the old landrace Chinese Spring and the elite Swiss spring wheat line ‘CH CampalaLr22a’. There was a high degree of sequence conservation between the two chromosomes. Analysis of large structural variations revealed four large insertions/deletions (InDels) of >100 kb. Based on the molecular signatures at the breakpoints, unequal crossing over and double-strand break repair were identified as the evolutionary mechanisms that caused these InDels. Three of the large InDels affected copy number of NLRs, a gene family involved in plant immunity. Analysis of single nucleotide polymorphism (SNP) density revealed three haploblocks of ~8 Mb, ~9 Mb and ~48 Mb with a 35-fold increased SNP density compared to the rest of the chromosome.ConclusionsThis comparative analysis of two high-quality chromosome assemblies enabled a comprehensive assessment of large structural variations. The insight obtained from this analysis will form the basis of future wheat pan-genome studies.
Modeling driver cells in developing neuronal networks
Authors: Luccioli Stefano , Angulo-Garcia David , Cossart Rosa , Malvache Arnaud , Módol Laura , Sousa Vitor Hugo , Bonifazi Paolo , Torcini Alessandro 
Published: February 2018

AbstractSpontaneous emergence of synchronized population activity is a characteristic feature of developing brain circuits. Recent experiments in the developing neo-cortex showed the existence of driver cells able to impact the synchronization dynamics when single-handedly stimulated. We have developed a spiking network model capable to reproduce the experimental results, thus identifying two classes of driver cells: functional hubs and low functionally connected (LC) neurons. The functional hubs arranged in a clique orchestrated the synchronization build-up, while the LC drivers were lately or not at all recruited in the synchronization process. Notwithstanding, they were able to alter the network state when stimulated by modifying the temporal activation of the functional clique or even its composition. LC drivers can lead either to higher population synchrony or even to the arrest of population dynamics, upon stimulation. Noticeably, some LC driver can display both effects depending on the received stimulus. We show that in the model the presence of inhibitory neurons together with the assumption that younger cells are more excitable and less connected is crucial for the emergence of LC drivers. These results provide a further understanding of the structural-functional mechanisms underlying synchronized firings in developing circuits possibly related to the coordinated activity of cell assemblies in the adult brain.Author SummaryThere is timely interest on the impact of peculiar neurons (driver cells) and of small neuronal sub-networks (cliques) on operational brain dynamics. We first provide experimental data concerning the effect of stimulated driver cells on the bursting activity observable in the developing entorhinal cortex. Secondly, we develop a network model able to fully reproduce the experimental observations. Analogously to the experiments two types of driver cells can be identified: functional hubs and low functionally connected (LC) drivers. We explain the role of hub neurons, arranged in a clique, for the orchestration of the bursting activity in control conditions. Furthermore, we report a new mechanism, which can explain why and how LC drivers emerge in the structural-functional organization of the enthorinal cortex.
TrackSig: reconstructing evolutionary trajectories of mutations in cancer
Authors: Rubanova Yulia , Shi Ruian , Harrigan Caitlin F , Li Roujia , Wintersinger Jeff , Sahin Nil , Deshwar Amit , Morris Quaid ,   PCAWG Evolution and Heterogeneity Working Group,   PCAWG network
Published: February 2018

ABSTRACTWe present a new method, TrackSig, to estimate the evolutionary trajectories of signatures of different somatic mutational processes from DNA sequencing data from a single, bulk tumour sample. TrackSig uses probability distributions over mutation types, called mutational signatures, to represent different mutational processes and detects the changes in the signature activity using an optimal segmentation algorithm that groups somatic mutations based on their estimated cancer cellular fraction (CCF) and their mutation type (e.g. CAG->CTG). We use two different simulation frameworks to assess both TrackSig’s reconstruction accuracy and its robustness to violations of its assumptions, as well as to compare it to a baseline approach. We find 2-4% median error in reconstructing the signature activities on simulations with varying difficulty with one to three subclones at an average depth of 30x. The size and the direction of the activity change is consistent in 83% and 95% of cases respectively. There were an average of 0.02 missed and 0.12 false positive subclones per sample. In our simulations, grouping mutations by mutation type (TrackSig), rather than by clustering CCF (baseline strategy), performs better at estimating signature activities and at identifying subclonal populations in the complex scenarios like branching, CNA gain, violation of infinite site assumption, and the inclusion of neutrally evolving mutations. TrackSig is open source software, freely available at https://github.com/morrislab/TrackSig.
Sexual isolation with and without ecological isolation in marine isopodsJ. albifronsandJ. praehirsuta
Authors: Ribardière Ambre , Pabion Elsa , Coudret Jérôme , Daguin-Thiébaut Claire , Houbin Céline , Loisel Stéphane , Henry Sébastien , Broquet Thomas 
Published: February 2018

AbstractSexual barriers associated with mate choice are nearly always found to be associated with some level of ecological isolation between species. The independence and relative strength of sexual isolation are thus difficult to assess. Here we take advantage of a pair of isopod species (Jaera albifronsandJ. praehirsuta) that show sexual isolation and coexist in populations where they share the same microhabitat or not (i.e. without or with ecological isolation). Using no-choice trials and a free-choice experimental population, we estimated the strength of sexual isolation betweenJ. albifronsandJ. praehirsutaindividuals originating from these different ecological contexts. We found that sexual isolation is strong in presence and absence of ecological isolation, but that it is asymmetric and fails to prevent gene flow entirely. First-generation post-zygotic barriers were low, and there was no sexual isolation withinJ. praehirsutaacross habitats. TheJ. albifrons/J. praehirsutaspecies pair thus provides an example where the role of sexual isolation as a barrier to gene flow i) does not depend upon current ecological isolation, ii) seems to have evolved independently of local ecological conditions, but iii) is insufficient to complete speciation entirely on its own.
Scopoletin Augments DJ1/Nrf2 Signalling and Prevents Protein Aggregation in Parkinson’s disease
Authors: Kishore Kumar S Narasimhan , Deepthy Jayakumar , Prema Velusamy , Ashokkumar Srinivasan , Thangarajeswari Mohan , Bhavani Ravi Divya , Saraswathi Uthamaraman , Yogesh Kanna Sathyamoorthy , Rajasekaran Namakal S. , Kalaiselvi Periandavan 
Published: February 2018

AbstractGiven the role of oxidative stress in PD pathogenesis and off-target side effects of currently available drugs, several natural phytochemicals seems to be promising in the management of PD. Here, we tested the hypothesis that scopoletin, an active principle obtained from Morinda citrifolia (MC), efficiently quenches oxidative stress through DJ-1/Nrf2 signalling and ameliorates rotenone-induced PD. Despite reducing the oxidative stress, administration of MC extract (MCE) has lessened the protein aggregation as evident from decreased levels of nitrotyrosine and α-Synuclein. In vitro studies revealed that scopoletin lessened rotenone-induced apoptosis in SH-SY5Y cells through preventing oxidative injury. Particularly, scopoletin markedly up-regulated DJ-1, which then promoted the nuclear translocation of Nrf2 and transactivation of antioxidant genes. Furthermore, we found that scopoletin prevent the nuclear exportation of Nrf2 by reducing the levels of Keap1 and thereby enhancing the neuronal defence system. Overall, our findings suggest that scopoletin acts through DJ-1 mediated Nrf2 signalling to protect the brain from rotenone-induced oxidative stress and PD. Thus, we postulate that scopoletin could be a potential drug to treat PD.
In situ administration of cytokine combinations induces tumor regression
Authors: Zhang Jinyu , Jiang Haochen , Zhang Yunhai 
Published: February 2018

AbstractRecent advances in cancer immunotherapy suggest a possibility of harnessing the immune system to defeat malignant tumors, but complex immunosuppressive microenvironment confined the therapeutic benefits to a minority of patients with solid tumors. Here we constructed a lentivector based inducible system to evaluate the therapeutic effect of cytokines in established tumors. Doxycycline (Dox) induced local expression of cytokine combinations exhibited strong synergistic effect, leading to complete regression of tumors. Notably, IL12+GMCSF+IL2 expression induced eradication of tumors in all mice tolerated with this treatment, including those bearing large tumors of ~15mm in diameter, and generated an intensive systemic antitumor immunity. Other combinations with similar immune regulatory roles also induced tumor elimination in a majority of mice. Moreover, intratumoral injection of chitosan/IL12+GMCSF+IL2 solution induced complete response in all tested syngeneic tumor models, regardless of various tumor immunograms. These results provide a versatile method for the immunotherapy of intractable malignant neoplasm.
Individual- and population-level drivers of consistent foraging success across environments
Authors: Snijders Lysanne , Kurvers Ralf H. J. M. , Krause Stefan , Ramnarine Indar W. , Krause Jens 
Published: February 2018

AbstractIndividual foraging is under strong natural selection. Yet, whether individuals differ consistently in their foraging success across environments, and which individual and population-level traits might drive such differences, is largely unknown. We addressed this question in a field experiment, conducting over 1,100 foraging trials with nine subpopulations of guppies,Poecilia reticulata, translocating them across environments in the wild. A-priori, we determined the individual social phenotypes. We show that individuals consistently differed in reaching food, but not control, patches across environments. Social individuals reached more food patches than less social ones and males reached more food patches than females. Overall, individuals were, however, more likely to join females at patches than males, which explains why individuals in subpopulations with relatively more females reached, on average, more food patches. Our results provide rare evidence for individual differences in foraging success across environments, driven by individual and population level (sex ratio) traits.
High carnivore population density highlights the conservation value of industrialised sites
Authors: Loock Daan J. E. , Williams Samual T. , Emslie Kevin W. , Matthews Wayne S. , Swanepoel Lourens H. 
Published: February 2018

AbstractAs the environment becomes increasingly altered by human development, the importance of understanding the ways in which wildlife interact with modified landscapes is becoming clear. Areas such as industrial sites are sometimes presumed to have little conservation value, but many of these sites have areas of less disturbed habitats around their core infrastructure, which could provide ideal conditions to support some species, such as mesocarnivores. We conducted the first assessments of the density of serval (Leptailurus serval) at the Secunda Synfuels Operations plant, South Africa. We ran three camera trap surveys to estimate serval density using a spatially explicit capture recapture framework. Servals occurred at densities of 76.20-101.21 animals per 100 km2, which are the highest recorded densities for this species, presumably due to high abundance of prey and the absence of persecution and/or competitor species. Our findings highlight the significant conservation potential of industrialised sites, and we suggest that such sites could help contribute towards meeting conservation goals.
Taxonomic Profiling and Populational Patterns of Bacterial Bile Salt Hydrolase (BSH) Genes on Worldwide Human Gut Microbiome
Authors: Song Ziwei , Cai Yuanyuan , Wang Xue , Lin Xiaoxuan , Cui Yingyun , Shang Jing , Jin Liang , Li Jing 
Published: February 2018

SummaryBile salt hydrolase (BSH) in gut bacteria can hydrolyze conjugated bile salts to unconjugated bile acids and amino acids. Thereby play a crucially important role in host health by reducing serum cholesterol levels, preserving bile acids balance and regulating various metabolism as signaling molecules. Here we present the taxonomic identification of BSHs in human microbiota and elucidate the abundance and activity differences of various bacterial BSHs among 11 different populations. For the first time, we have revealed BSH are distributed in 154 intestinal bacterial strains within 33 genera in human microbiota. However, these BSHs present obviously differentiation for the sequence identity being from 28.6% to 100%, and the 32.7% bacteria strains having more than one paralogs of BSHs with dissimilarity. Therefore, we reclassified the BSHs from the different genera into 6 phylotypes basing on their phylogenetic tree, and demonstrate the significant abundance patterns of BSH phylotypes among different populations. From the enzyme activity comparison, the representative sequence of BSH-T3 was shown highest enzyme activity in 6 phylotypes. Meanwhile, BSH-T3 sequences which all distributed inLactobacillusshow highest abundance in Chinese and Austrian. The information illustrated by this study is useful for investigating the population differences of bile acid metabolism related diseases, and further giving a new suggestion on selection of probiotics or development of pharmaceutical proteins based upon the activity of BSH phylotypes to regulate host metabolism and maintain fitness.
Naked mole-rat brain neurons are resistant to acid-induced cell death
Authors: Husson Zoé , Smith Ewan St John 
Published: February 2018

AbstractRegulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na+permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs,Heterocephalus glaber) are long-lived, fossorial, eusocial rodents that display remarkable behavioral/cellular hypoxia and hypercapnia resistance. In the central nervous system, ASIC subunit expression is similar between mouse and NMR with the exception of much lower expression of ASIC4 throughout the NMR brain. However, ASIC function and neuronal sensitivity to sustained acidosis has not been examined in the NMR brain. Here, we show with whole-cell patch-clamp electrophysiology of cultured NMR and mouse cortical and hippocampal neurons that NMR neurons have smaller voltage-gated Na+channel currents and more hyperpolarized resting membrane potentials. We further demonstrate that acid-mediated currents in NMR neurons are of smaller magnitude than in mouse, and that all currents in both species are fully blocked by the ASIC antagonist benzamil. We further demonstrate that NMR neurons show greater resistance to acid-induced cell death than mouse neurons. In summary, NMR neurons show significant cellular resistance to acidotoxicity compared to mouse neurons, contributing factors likely to be smaller ASIC-mediated currents and reduced NaV activity.AbbreviationsASIC, acid-sensing ion channel; CNS, central nervous system; DRG, dorsal root ganglion; NaV, voltage-gated Na+channel; NMR, naked mole-rat; TTX, tetrodotoxin