bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling of Ion and Water Transport in the Biological Nanopore ClyA
Authors: Willems Kherim , Ruić Dino , Lucas Florian , Barman Ujjal , Hofkens Johan , Maglia Giovanni , Van Dorpe Pol 
Published: January 2020

AbstractIn recent years, the protein nanopore cytolysin A (ClyA) has become a valuable tool for the detection, characterization and quantification of biomarkers, proteins and nucleic acids at the single-molecule level. Despite this extensive experimental utilization, a comprehensive computational study of ion and water transport through ClyA is currently lacking. Such a study yields a wealth of information on the electrolytic conditions inside the pore and on the scale the electrophoretic forces that drive molecular transport. To this end we have built a computationally efficient continuum model of ClyA which, together with an extended version of Poison-Nernst-Planck-Navier-Stokes (ePNP-NS) equations, faithfully reproduces its ionic conductance over a wide range of salt concentrations. These ePNP-NS equations aim to tackle the shortcomings of the traditional PNP-NS models by self-consistently taking into account the influence of both the ionic strength and the nanoscopic scale of the pore on all relevant electrolyte properties. In this study, we give both a detailed description of our ePNP-NS model and apply it to the ClyA nanopore. This enabled us to gain a deeper insight into the influence of ionic strength and applied voltage on the ionic conductance through ClyA and a plethora of quantities difficult to assess experimentally. The latter includes the cation and anion concentrations inside the pore, the shape of the electrostatic potential landscape and the magnitude of the electro-osmotic flow. Our work shows that continuum models of biological nanopores—if the appropriate corrections are applied—can make both qualitatively and quantitatively meaningful predictions that could be valuable tool to aid in both the design and interpretation of nanopore experiments.
Conserved and divergent features of DNA methylation in embryonic stem cell-derived neurons
Authors: Martin Sally , Poppe Daniel , Olova Nelly , O’Leary Conor , Ivanova Elena , Pflueger Jahnvi , Dechka Jennifer , Simmons Rebecca K. , Cooper Helen M. , Reik Wolf , Lister Ryan , Wolvetang Ernst J. 
Published: January 2020

AbstractDNA methylation functions in genome regulation and is implicated in neuronal maturation. Early post-natal accumulation of atypical non-CG methylation (mCH) occurs in neurons of mice and humans, but its precise function remains unknown. Here we investigate mCH deposition in neurons derived from mouse ES-cellsin vitroand in cultured primary mouse neurons. We find that both acquire comparable levels of mCH over a similar period asin vivo. In vitromCH deposition occurs concurrently with a transient increase inDnmt3aexpression, is preceded by expression of the post-mitotic neuronal markerRbfox3(NeuN) and is enriched at the nuclear lamina. Despite these similarities, whole genome bisulfite sequencing reveals that mCH patterning in mESC-derived neurons partially differs fromin vivo. mESC-derived neurons therefore represent a valuable model system for analyzing the mechanisms and functional consequences of correct and aberrantly deposited CG and non-CG methylation in neuronal maturation.
The draft genome of the endangered, relictual plantKingdonia uniflora(Circaeasteraceae, Ranunculales) reveals potential mechanisms and perils of evolutionary specialization
Authors: Sun Yanxia , Deng Tao , Zhang Aidi , Moore Michael J. , Landis Jacob B. , Lin Nan , Zhang Huajie , Zhang Xu , Huang Jinling , Zhang Xiujun , Sun Hang , Wang Hengchang 
Published: January 2020

AbstractKingdonia uniflora, an alpine herb, has an extremely narrow distribution and represents a model for studying evolutionary mechanisms of species that have adapted to undisturbed environments for evolutionary long periods of time. We assembled a 1,004.7-Mb draft genome (encoding 43,301 genes) and investigated the evolutionary history ofK. uniflora, along with mechanisms related to its endangered status. Phylogenomic analyses based on 497 single copy genes confirmed the sister relationship betweenK. unifloraandCircaeaster agrestis, which were estimated to have diverged around 52 Mya. Proliferation of LTR retrotransposons inK. uniflorais estimated to occur around 2.7 Mya, coinciding with one recent uplift of the Hengduan Mountains between the late Miocene and late Pliocene. Across 12 species of monocots, early-diverging eudicots and core eudicots,K. uniflorashowed significant overrepresentation in gene families associated with DNA repair and underrepresentation in gene families associated with stress response. Most of the plastidndhgenes were found to be lost not only in the plastome but also in the nuclear genome ofK. uniflora. During the evolutionary process, the overrepresentation of gene families involved in DNA repair could help asexualK. uniflorareduce the accumulation of deleterious mutations, while at the same time, reducing genetic diversity which is important in responding to environment fluctuations. The underrepresentation of gene families related to stress response and functional loss ofndhgenes could be due to lack or loss of ability to respond to environmental changes caused by long-term adaptation to a relatively stable ecological environment.
The formation of microbial exoskeletons is driven by a controlled calcium-concentrating subcellular niche
Authors: Keren-Paz Alona , Cohen-Cymberknoh Malena , Kolodkin-Gal Dror , Peretz Shani , Karunker Iris , Wolf Sharon G. , Olender Tsviya , Kapishnikov Sergey , Brumfield Vlad , Dersch Simon , Kartvelishvily Elena , Green-Zelinger Peninnah , Isola-Adeyanju Damilola , Suissa Ronit , Shteinberg Michal , McLeod Daniel , Patrauchan Marianna , Zamir Gideon , Gal Assaf , Graumann Peter L. , Kerem Eitan , Kolodkin-Gal Ilana 
Published: January 2020

AbstractIn nature, bacteria reside in biofilms - multicellular differentiated communities held together by extracellular matrix. In this work, we identified a novel subpopulation essential for biofilm formation – mineral-forming cells. This subpopulation contains an intracellular calcium-accumulating niche, in which the formation of a calcium carbonate mineral is initiated. As the biofilm colony develops, this mineral grows in a controlled manner, forming a functional macrostructure that serves the entire community.The molecular mechanisms promoting calcite scaffold formation were conserved between three distant phyla – the Gram-positiveBacillus subtilis, Gram-negativePseudomonas aeruginosaand the actinobacteriumMycobacterium abscessus. Biofilm development of all three species was similarly impaired by inhibition of calcium uptake and carbonate accumulation. Moreover, chemical inhibition and mutations targeting mineralization both significantly reduced the attachment ofP. aeruginosato the lung, as well as the subsequent damage inflicted by biofilms to lung tissues, and restored their sensitivity to antibiotics.The evolutionary conserved cellular pathway controlling the fundamental feature of biofilm development uncovered in this work offers novel druggable targets for antibiotics to combat otherwise untreatable biofilm infections.
Vitamin B12is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
Authors: Queiroz Karina Barbosa de , Cavalcante-Silva Vanessa , Lopes Flávia Lombardi , Rocha Gifone Aguiar , D’Almeida Vânia , Coimbra Roney Santos 
Published: January 2020

AbstractBackgroundBacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl and its homeostasis can be modulated by vitamin B12, cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin B12adjuvant therapy were assessed in an infant rat model of BM.MethodsEleven-day old rats were intracysternally infected withStreptococcus pneumoniaeserotype 3, or saline, treated with B12or placebo, and, 24h after infection, their hippocampi were analyzed for apoptosis in the dentate gyrus, sulfur amino acids content, global DNA methylation, transcription and proximal promoter methylation of candidate genes. Differences between groups were compared using 2-way ANOVA 2-way followed by Bonferroni post-hoc test. Correlations were tested with Spearman’s test.ResultsB12attenuated BM-induced hippocampal apoptosis in a Hcy dependent manner (r = 0.80,P< 0.05). BM caused global DNA hypomethylation, however B12restored this parameter. Accordingly, B12increased the methylation capacity of hippocampal cells from infected animals, as inferred from the ratio S-adenosyl methionine (SAM):S-adenosyl homocysteine (SAH) in infected animals. BM upregulated selected pro-inflammatory genes, and this effect was counteracted by B12, which also increased methylation of CpGs at the promoter ofCcl3of infected animals.ConclusionHcy is likely to play a central role in hippocampal damage in the infant rat model of BM, and B12shows an anti-inflammatory and neuroprotective action through methyl-dependent epigenetic mechanisms.
Bacterial carotenoids suppressCaenorhabditis eleganssurveillance and defense of translational dysfunction
Authors: Govindan J. Amaranath , Jayamani Elamparithi , Lelyveld Victor , Szostak Jack , Ruvkun Gary 
Published: January 2020

AbstractMicrobial toxins and virulence factors often target the eukaryotic translation machinery.Caenorhabditis eleganssurveils for such microbial attacks by monitoring translational competence, and if a deficit is detected, particular drug detoxification and bacterial defense genes are induced. The bacteriaKocuria rhizophilahas evolved countermeasures to animal translational surveillance and defense pathways. Here, we used comprehensive genetic analysis ofKocuria rhizophilato identify the bacterial genetic pathways that inhibitC. eleganstranslational toxin surveillance and defense.Kocuria rhizophilamutations that disrupt its ability to disable animal immunity and defense map to multiple steps in the biosynthesis of a 50-carbon bacterial carotenoid from 5 carbon precursors. Extracts of the C50carotenoid from wild typeK. rhizophilacould restore this bacterial anti-immunity activity toK. rhizophilacarotenoid biosynthetic mutant.Corynebacterium glutamicum,also inhibits theC. eleganstranslation detoxification response by producing the C50carotenoid decaprenoxanthin, andC. glutamicumcarotenoid mutants are defective in this suppression ofC. elegansdetoxification. Consistent with the salience of these bacterial countermeasures to animal drug responses, bacterial carotenoids sensitizeC. elegansto drugs that target translation and inhibit food aversion behaviors normally induced by protein translation toxins or mutations. The surveillance and response to toxins is mediated by signaling pathways conserved across animal phylogeny, suggesting that these bacterial carotenoids may also suppress such human immune and toxin responses.
Lack of intrinsic postzygotic isolation in haplodiploid male hybrids despite high genetic distance
Authors: Bendall Emily E. , Mattingly Kayla M. , Moehring Amanda J. , Linnen Catherine R. 
Published: January 2020

AbstractEvolutionary biologists have long been interested in understanding the mechanisms underlying Haldane’s rule. The explanatory theories of dominance and faster-X, which are based on recessive alleles being expressed in the heterogametic sex, have been proposed as common mechanisms. These mechanisms predict that greater hemizygosity leads to both faster evolution and greater expression of intrinsic postzygotic isolation. Under these mechanisms, haplodiploids should evolve and express intrinsic postzygotic isolation faster than diploids because the entire genome is analogous to a sex chromosome. Here, we measure sterility and inviability in hybrids betweenNeodiprion pinetumandN. lecontei, a pair of haplodiplopids that differ morphologically, behaviorally, and genetically. We compare the observed isolation to that expected from published estimates of isolation in diploids at comparable levels of genetic divergence. We find that both male and female hybrids are viable and fertile, which is less isolation than expected. We then discuss several potential explanations for this surprising lack of isolation, including alternative mechanisms for Haldane’s rule and a frequently overlooked quirk of haplodiploid genetics that may slow the emergence of complete intrinsic postzygotic isolation in hybrid males. Finally, we describe how haplodiploids, an underutilized resource, can be used to differentiate between mechanisms of Haldane’s rule.
Data augmentation based on dynamical systems for the classification of brain states
Authors: Perl Yonatan Sanz , Pallavicini Carla , Ipiña Ignacio Perez , Kringelbach Morten , Deco Gustavo , Laufs Helmut , Tagliazucchi Enzo 
Published: January 2020

AbstractThe application of machine learning algorithms to neuroimaging data shows great promise for the classification of physiological and pathological brain states. However, classifiers trained on high dimensional data are prone to overfitting, especially for a low number of training samples. We describe the use of whole-brain computational models for data augmentation in brain state classification. Our low dimensional model is based on nonlinear oscillators coupled by the empirical SC of the brain. We use this model to enhance a dataset consisting of functional magnetic resonance imaging recordings acquired during all stages of the human wake-sleep cycle. After fitting the model to the average FC of each state, we show that the synthetic data generated by the model yields classification accuracies comparable to those obtained from the empirical data. We also show that models fitted to individual subjects generate surrogates with enough information to train classifiers that present significant transfer learning accuracy to the whole sample. Whole-brain computational modeling represents a useful tool to produce large synthetic datasets for data augmentation in the classification of certain brain states, with potential applications to computer-assisted diagnosis and prognosis of neuropsychiatric disorders.
An interaction network of RNA-binding proteins involved inDrosophilaoogenesis
Authors: Bansal Prashali , Madlung Johannes , Schaaf Kristina , Macek Boris , Bono Fulvia 
Published: January 2020

AbstractDuringDrosophilaoogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from wholeDrosophilaovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.
Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy
Authors: Geck Renee C. , Foley Jackson R. , Stewart Tracy R. Murray , Asara John M. , Casero Robert A. , Toker Alex 
Published: January 2020

AbstractTreatment of triple-negative breast cancer (TNBC) is limited by a lack of effective molecular targeted therapies. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. We found that exposure of TNBC cells to cytotoxic chemotherapy drugs leads to alterations in arginine and polyamine metabolites due to a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme ornithine decarboxylase (ODC). The reduction in ODC was mediated by its negative regulator, antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor DFMO sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines showed greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. Alterations in polyamine metabolism in response to chemotherapy, as well as preferential sensitization of TNBC cells to chemotherapy by DFMO, suggest that ODC may be a targetable metabolic vulnerability in TNBC.
MSIsensor-pro: fast, accurate and matched-normal-sample-free detection of microsatellite instability
Authors: Jia Peng , Yang Xiaofei , Guo Li , Liu Bowen , Lin Jiadong , Liang Hao , Sun Jianyong , Zhang Chengsheng , Ye Kai 
Published: January 2020

ABSTRACTWe developed MSIsensor-pro (https://github.com/xjtu-omics/msisensor-pro), an open-source single sample microsatellite instability (MSI) scoring method for research and clinical applications. MSIsensor-pro introduces a multinomial distribution model to quantify polymerase slippages for each tumor sample and a discriminative sites selection method to enable MSI detection without matched normal samples. For samples of various sequencing depths and tumor purities, MSIsensor-pro significantly outperformed the current leading methods in terms of both accuracy and computational cost.
Discovery of a Novel Inhibitory Neuron Class, the L-Stellate Cells of the Cochlear Nucleus
Authors: Ngodup Tenzin , Romero Gabriel E. , Trussell Laurence O. 
Published: January 2020

AbstractAuditory processing depends upon inhibitory signaling by interneurons, even at its earliest stages in the ventral cochlear nucleus (VCN). Remarkably, to date only a single subtype of inhibitory neuron has been documented in the VCN, a projection neuron termed the D-stellate cell. With the use of a transgenic mouse line, optical clearing and imaging techniques, combined with electrophysiological tools, we revealed a population of glycinergic cells in the VCN distinct from the D-stellate cell. These novel multipolar glycinergic cells were smaller in soma size and dendritic area, but over 10-fold more numerous than D-stellate cells. They were activated by auditory nerve fibers and T-stellate cells, and made local inhibitory synaptic contacts on principal cells of the VCN. Given their abundance, combined with their narrow dendritic fields and axonal projections, it is likely that these neurons, here termed L-stellate cells, play a significant role in frequency-specific processing of acoustic signals.
A study on the influence of street food authenticity and degree of their variations on the tourists’ overall destination experiences
Authors: Gupta Vikas , Sajnani Manohar 
Published: January 2020

PurposeThe purpose of this paper is to find out how the overall destination experiences of the foreign tourists in India are influenced by the perceived authenticity of the street foods and the degree of their variation/modification. It will also discuss how these characteristics further influence the tourists’ behavioural intentions (intention to revisit and word-of-mouth).Design/methodology/approachData have been collected from 263 foreign tourists visiting Delhi at various street food vending sites using location intercept technique through structured questionnaire. Different ad hoc scales were adapted based on previous studies for measuring the perception of authenticity, ability to adapt, cultural disparity and overall perceived experience. The partial least squares method was applied to achieve the dual estimation of the measurement and the structural model.FindingsResult indicates that perceived authenticity and cultural disparity have a positive influence on the overall perceived experiences of the foreign tourists. It is also found that the degree of variation/modification in the street foods condenses the authenticity perception of the tourists. Findings reveal that the tourists are less influenced by the cultural disparity when they are able to adapt to diverse cultures and simultaneously authenticity have a larger effect on their overall destination experiences.Originality/valueAlthough various studies have been conducted in the past related to the food experiences of tourists at various destinations, this will be the first attempt to find out how the overall destination experiences of the foreign tourists in India are influenced by the perceived authenticity of the street foods and the degree of their variation/adaptation. It will help the stakeholders to appropriately align the gastronomic product and enhance the tourists’ overall destination experiences.
Influence of digital learning orientation and readiness for change on innovative work behaviour: reflections from the higher education sector
Authors: Aboobaker Nimitha , K.A. Zakkariya 
Published: January 2020

PurposeThe paper aims to examine the influence of students’ digital learning orientation on their readiness for change and innovative work behaviour. Elaborations are made on how these concepts can be utilized for strengthening the teaching-learning process in higher education institutions, and help them gain more cutting-edge competencies in areas of learning delivery and learning engagement.Design/methodology/approachThe respondents for this descriptive study were drawn through random sampling, from an end-semester student group, who had taken up post-graduate courses in science and technology streams of a prominent science and technology university. Data was collected by administering self-reporting questionnaires.FindingsThe study revealed that higher digital learning orientation is associated with improved attitude towards change and higher innovative behaviour. With conflicting results in exiting literature, regarding the influence of digital learning orientation on learning outcomes, this study adds to the body of knowledge by testing previously unexplored propositions in a student sample.Originality/valueThis study is pioneering in conceptualizing and testing the proposed model. The paper emphasizes the role of digital learning orientation, especially in the context of today’s students being referred to as ‘digital natives’. It is thus imperative to understand how the same can be translated into learning outcomes. The results of the study highlights the need for augmenting the role of digital orientation in the teaching-learning process, so as to transform educational institutions sustainable in producing graduates with readiness for change and innovative work behaviour, in the context of an emergent digital economy.