bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for a potential role of miR-1908-5p and miR-3614-5p in autoimmune disease risk using genome-wide analyses
Authors: Wohlers Inken , Bertram Lars , Lill Christina M. 
Published: March 2018

AbstractGenome-wide association studies (GWAS) have identified a large number of genetic risk loci for autoimmune diseases. However, the functional variants underlying these disease associations remain largely unknown. There is evidence that microRNA-mediated regulation may play an important role in this context. Therefore, we assessed whether autoimmune disease loci unfold their effects via altering microRNA expression in relevant immune cells.To this end, we performed microRNA expression quantitative trait loci (eQTL) analyses across 115 GWAS regions associated with 12 autoimmune diseases using next-generation sequencing data of 345 lymphoblastoid cell lines. Statistical analyses included the application and extension of a recently proposed framework (joint likelihood mapping), to microRNA expression data and microRNA target gene enrichment analyses of relevant GWAS data.Overall, only a minority of autoimmune disease risk loci may exert their pathophysiologic effects by altering miRNA expression based on JLIM. However, detailed functional fine-mapping revealed two independent GWAS regions harboring autoimmune disease risk SNPs with significant effects on microRNA expression. These relate to SNPs associated with Crohn’s disease (CD; rs102275) and rheumatoid arthritis (RA; rs968567), which affect the expression of miR-1908-5p (prs102275=1.44e-20, prs968567=2.54e-14). In addition, an independent CD risk SNP, rs3853824, was found to alter the expression of miR-3614-5p (p=5.70e-7). To support these findings, we demonstrate that GWAS signals for RA and CD were enriched in genes predicted to be targeted by both miRNAs (all with p<0.05).In summary, our study points towards a pathophysiological role of miR-1908-5p and miR- 3614-5p in autoimmunity.
Weak and equally balanced synaptic inputs to interneurons in the CA1 hippocampus characterize in vivo rhythmic states
Authors: Guet-McCreight Alexandre , Skinner Frances K. 
Published: March 2018

AbstractBrain coding strategies are enabled by the balance of synaptic inputs that individual neurons receive as determined by the networks in which they reside. Inhibitory cell types contribute to brain function in distinct ways but recording from specific, inhibitory cell types during behaviour to determine their contributions is difficult. In particular, the in vivo activities of vasoactive intestinal peptide-expressing interneuron specific 3 (IS3) cells in the hippocampus that only target other inhibitory cells are unknown at present. We perform a massive, computational exploration of possible synaptic inputs to IS3 cells using multi-compartment models and optimized synaptic parameters. We find that asynchronous in vivo-like states that are sensitive to additional theta-timed inputs exist when excitatory and inhibitory synaptic conductances are equally balanced and there are low amounts of correlated inputs. Thus, using a generally applicable computational approach we predict the existence of balanced states in hippocampal circuits during rhythmic activities.
Agricultural fungicides inadvertently influence the fitness of Colorado potato beetles,Leptinotarsa decemlineata, and their susceptibility to insecticides
Authors: Clements Justin , Schoville Sean , Clements Anna , Amezian Dries , Davis Tabatha , Sanchez-Sedillo Benjamin , Bradfield Christopher , Huseth Anders S. , Groves Russell L. 
Published: March 2018

AbstractThe Colorado potato beetle (CPB),Leptinotarsa decemlineata(Say), is an agricultural pest of solanaceous crops which has developed insecticide resistance at an alarming rate. Up to this point, little consideration has been given to unintended, or inadvertent effects that non-insecticide xenobiotics may have on insecticide susceptibility inL. decemlineata. Fungicides, such as chlorothalonil and boscalid, are often used to control fungal pathogens in potato fields and are applied at regular intervals whenL. decemlineatapopulations are present in the crop. In order to determine whether fungicide use may be associated with elevated levels of insecticide resistance inL. decemlineata, we examined phenotypic responses inL. decemlineatato the fungicides chlorothalonil and boscalid. Using enzymatic and transcript abundance investigations we also examined modes of molecular detoxification in response to both insecticide (imidacloprid) and fungicide (boscalid and chlorothalonil) application to more specifically determine if fungicides and insecticides induce similar metabolic detoxification mechanisms. Both chlorothalonil and boscalid exposure induced a phenotypic, enzymatic and transcript response inL. decemlineatawhich correlates with known mechanisms of insecticide resistance.Key MessagesPrior-exposure to a fungicidal application changes the phenotypic response ofLeptinotarsa decemlineatato the insecticide imidaclopridBoth a fungicide and insecticide application activates similar molecular mechanisms of detoxification inLeptinotarsa decemlineataFungicidal xenobiotics may contribute to insecticide resistance inLeptinotarsa decemlineataAuthor Contribution StatementJC, SS, CB, AH, and RG conceived and designed research. JC, AC, DA, TD, and BS conducted experiments. JC and AC analyzed data. JC and RG wrote the manuscript. All authors read and approved the manuscript.
Scute structure reveals sex of juvenile and young sturgeon in caviar aquaculture technology
Authors: Barulin Nikolai V. 
Published: March 2018

AbstractSturgeons are valued as specialty black caviar, which is very expensive. Only females are used in the technology of caviar aquaculture. Universal method of sex determination has not yet been developed. Most of known methods are not sufficiently accurate, or used at a relatively late age, or difficult to use. Perfect early determination of sex is considered to be impossible. Because of the dark color of most sturgeon, important morphological differences, which fish of almost all ages have, were overlooked. We first found that the scute structure of Sterlet and Siberian sturgeon depends on the sex, such a pattern is typical for sturgeon of all ages. We found that sex determination is possible at very early stages. Dependencies found with the help of machine learning method open a possibility for creation of sex determination equipment using the artificial intelligence. Our results open a perspective for creation of the sex determination methods for other 23 sturgeon species, which can increase the efficiency of caviar aquaculture and sturgeon restoration in natural waters.
Overexpression of RsMYB1 enhances heavy metal stress tolerance in transgenic petunia by elevating the transcript levels of stress tolerant and antioxidant genes
Authors: Ai Trinh Ngoc , Naing Aung Htay , Yun Byung-Wook , Kim Chang Kil 
Published: March 2018

AbstractThe RsMYB1 transcription factor (TF) controls the regulation of anthocyanin in radish (Raphanus sativus), and its overexpression in tobacco and petunia strongly enhances anthocyanin production. However, no data exists on whether RsMYB1 is involved in the mechanism that leads to abiotic stress tolerance. Under normal conditions, transgenic petunia plants expressing RsMYB1 and WT were able to thrive by producing well-developed broad leaves and regular roots. In contrast, a reduction in plant growth was observed when they were exposed to heavy metals (CuSO4, ZnSO4, MnSO4, and K2Cr2O7). However, RsMYB1-overexpressing plants were found to be more tolerant to the stresses than the WT plants because the expressions of stress tolerant genes (GSH and PCs) and antioxidant genes (SOD, CAT, and POX) were enhanced. In addition, according to the phylogenetic analysis, RsMYB1 has a strong sequence similarity with other MYB TFs that confer different abiotic stresses. These results suggest that overexpression of RsMYB1 enhances the expression levels of metal-induced stress tolerance genes and antioxidant genes, and the resultant increase in gene expression improves heavy metal stress tolerance in petunia.
Characterisation of molecular motions in cryo-EM single-particle data by multi-body refinement in RELION
Authors: Nakane Takanori , Kimanius Dari , Lindahl Erik , Scheres Sjors H.W. 
Published: March 2018

AbstractMacromolecular complexes that exhibit continuous forms of structural flexibility pose a challenge for many existing tools in cryo-EM single-particle analysis. We describe a new tool, called multi-body refinement, which models flexible complexes as a user-defined number of rigid bodies that move independently from each other. Using separate focused refinements with iteratively improved partial signal subtraction, the new tool generates improved reconstructions for each of the defined bodies in a fully automated manner. Moreover, using principal component analysis on the relative orientations of the bodies over all particles in the data set, we generate movies that describe the most important motions in the data. Our results on two test cases, a cytoplasmic ribosome from Plasmodium falciparum, and the spliceosomal B-complex from yeast, illustrate how multi-body refinement can be useful to gain unique insights into the structure and dynamics of large and flexible macromolecular complexes.Please note that this bioRxiv submission is ahead of the availability of the multi-body software in relion-3.0. We take great care in distributing stable software, but this does take time. We will announce the (beta-)release of relion-3.0 through the ccp-em mailing list (https://www.jiscmail.ac.uk/CCPEM) and on twitter (@SjorsScheres).
Substrate channeling in oxylipin biosynthesis through a protein complex in the plastid envelope ofArabidopsis thaliana
Authors: Pollmann Stephan , Springer Armin , Rustgi Sachin , von Wettstein Diter , Kang ChulHee , Reinbothe Christiane , Reinbothe Steffen 
Published: March 2018

ABSTRACTOxygenated membrane fatty acid derivatives dubbed oxylipins play important roles in the plant’s defense against biotic and abiotic cues. Plants challenged by insect pests, for example, synthesize a blend of different defense compounds that, amongst others, comprise volatile aldehydes and jasmonic acid (JA). Because all oxylipins are derived from the same pathway, we asked how their synthesis might be regulated and focused on two closely related, atypical cytochrome P450 enzymes designated CYP74A and CYP74B, i.e., allene oxide synthase (AOS) and hydroperoxide lyase (HPL). Both enzymes compete for the same substrate but give rise to different products. While the final product of the AOS branch is JA, those of the HPL branch comprise volatile aldehydes and alcohols. AOS and HPL are plastid envelope enzymes inArabidopsis thalianabut accumulate at different locations. Biochemical experiments identified AOS as constituent of complexes also containing lipoxygenase 2 (LOX2) and allene oxide cyclase (AOC), which catalyze consecutive steps in JA precursor biosynthesis, while excluding the concurrent HPL reaction. Based on published X-ray data, the structure of this complex could be modelled and amino acids involved in catalysis and subunit interactions identified. Genetic studies identified the microRNA 319 (miR319)-regulated clade of TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) transcription factor genes and CORONATINE INSENSITIVE 1 (COI1) to control JA production through the AOS-LOX2-AOC2 complex. Together, our results define a molecular branch point in oxylipin biosynthesis that allows fine-tuning the plant’s defense machinery in response to biotic and abiotic stimuli.
Symbiosis-related genes sustain the development of a downy mildew pathogen onArabidopsis thaliana
Authors: Ried Martina K. , Banhara Aline , Binder Andreas , Hwu Fang-Yu , Gust Andrea A. , Höfle Caroline , Hückelhoven Ralph , Nürnberger Thorsten , Parniske Martin 
Published: March 2018

AbstractThe interfaces through which nutrients are transferred from plant cells to arbuscular mycorrhiza fungi and biotrophic hyphal pathogens are structurally similar. We report that inArabidopsis thaliana, mutations in homologs of common symbiosis genes (CSGs) encoding homologs of the symbiosis receptor kinase SYMRK, the nucleoporins NUP133 and SEC13 or the cation channel POLLUX reduce the reproductive success ofHyaloperonospora arabidopsidis (Hpa).Analysis of the multiplication of extracellular bacterial pathogens,Hpa-induced cell death or callose accumulation, as well asHpa-or flg22-induced defence marker gene expression, did not reveal any traces of constitutive or exacerbated defence responses. We discovered an age-dependent, possibly senescence-related transition of haustorial shape that occurred significantly earlier and at higher frequency in the CSG mutants. These findings point to a function of the homologs of common symbiosis genes in haustorial maintenance thus revealing an overlapping gene set for the intracellular accommodation of hyphal symbionts and pathogens.
Intronic miRNA Mediated Gene Expression Regulation Controls Protein Crowding Inside the Cell
Authors: Sinha Prashant , Jaiswal Pragya , Jainarayanan Ashwin K. , Brahmachari Samir K. 
Published: March 2018

SUMMARYGene regulatory effects of microRNAs at a posttranscriptional level has been established over the last decade. In this study, we analyze the interaction networks of mRNA translation regulation through intronic miRNA, under various tissue-specific cellular contexts, taking into account the thermodynamic affinity, kinetics, and the presence of competitive interactors. This database, and analysis has been made available through an open-access web-server, miRiam, to promote further exploration.Here we report that expression of genes involved in Apoptosis Processes, Immune System Processes, Translation Regulator Activities, and Molecular Transport Activities within the cell are predominately regulated by miRNA mediation. Our findings further indicate that this regulatory effect has a profound effect in controlling protein crowding inside the cell. A miRNA mediated gene expression regulation serves as a temporal regulator, allowing the cellular machinery to temporarily ‘pause’ the translation of mRNA, indicating that the miRNA–mRNA interactions may be important for governing the optimal usage of cell volume.
Common antigenic motif recognized by human VH5-51/VL4-1 tau antibodies with distinct functionalities
Authors: Apetri Adrian , Crespo Rosa , Juraszek Jarek , Pascual Gabriel , Janson Roosmarijn , Zhu Xueyong , Zhang Heng , Keogh Elissa , Holland Trevin , Wadia Jay , Verveen Hanneke , Siregar Berdien , Mrosek Michael , Taggenbrock Renske , van Ameijde Jeroen , Inganäs Hanna , van Winsen Margot , Koldijk Martin H. , Zuijdgeest David , Borgers Marianne , Dockx Koen , Stoop Esther J.M. , Yu Wenli , Brinkman-van der Linden Els C. , Ummenthum Kimberley , van Kolen Kristof , Mercken Marc , Steinbacher Stefan , de Marco Donata , Hoozemans Jeroen J. , Wilson Ian A. , Koudstaal Wouter , Goudsmit Jaap 
Published: March 2018

ABSTRACTMisfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer’s Disease (AD). By interrogating IgG+ memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated VH5-51/VL4-1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of VH5-51 and VL4-1 recognizes a common Pro-Xn-Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD.
Smart Region-Growing: a novel algorithm for the segmentation of 3D clarified confocal image stacks
Authors: Callara Alejandro Luis , Magliaro Chiara , Ahluwalia Arti , Vanello Nicola 
Published: March 2018

AbstractMotivationAccurately mapping the brain at the micro-scale is still a challenge in cellular neuroscience. While notable success has been reached in the field of tissue clarification and confocal imaging to obtain high-fidelity maps of three-dimensional neuron organization, neuron segmentation is still far away of ground-truth and manual segmentation performed by experts may be needed. The need of an expert is in part related to the limited success of the algorithms and tools performing single-neuron segmentation from 3D microscopic image data available in the State of Art, in part to the non-complete information given by these methods, which typically perform neuron tracing and thus limit the interpret-ability of results.ResultsIn this paper, a novel algorithm for segmenting single neurons in their own arrangement within the brain is presented. The algorithm performs a region growing procedure with local thresholds based on the pixel intensity statistics typical of confocal acquisitions of biological samples and described by a mixture model. The algorithm is developed and tested on 3D confocal datasets obtained from clarified tissues. We compare the result of our algorithm with those obtained by manual segmentation performed by 6 different experts in terms of neuron surface area, volume and Sholl profiles. Statistical analysis performed on morphologic features extracted from the segmented structures confirms the feasibility of our approach.AvailabilityThe Smart Region Growing (SmRG) algorithm used in the analysis along with test confocal image stacks is available on request to the authors.Contactalejandrocallara@gmail.comSupplementary informationSupplementary data are available on request to the authors.
The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors
Authors: Selkrig Joel , Mohammad Farhan , Ng Soon Hwee , Yi Chua Jia , Tumkaya Tayfun , Ho Joses , Chiang Yin Ning , Rieger Dirk , Pettersson Sven , Helfrich-Förster Charlotte , Yew Joanne Y. , Claridge-Chang Adam 
Published: March 2018

AbstractIn animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species. We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing, control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over several behaviors fundamental to the animal’s survival and reproduction. The impact of commensal microbes on animal behaviour may not be broadly conserved.
Crystallographic observation of nonenzymatic RNA primer extension
Authors: Zhang Wen , Walton Travis , Li Li , Szostak Jack W. 
Published: March 2018

ABSTRACTThe importance of genome replication has inspired detailed crystallographic studies of enzymatic DNA/RNA polymerization. In contrast, the mechanism of nonenzymatic polymerization is less well understood, despite its critical role in the origin of life. Here we report the direct observation of nonenzymatic RNA primer extension through time-resolved crystallography. We soaked crystals of an RNA primer-template-dGMP complex with guanosine-5′-phosphoro-2-aminoimidazolide for increasing times. At early times we see the activated ribonucleotides bound to the template, followed by formation of the imidazolium-bridged dinucleotide intermediate. At later times, we see a new phosphodiester bond forming between the primer and the incoming nucleotide. The intermediate is pre-organized because of the constraints of base-pairing with the template and hydrogen bonding between the imidazole amino group and both flanking phosphates. Our results provide atomic-resolution insight into the mechanism of nonenzymatic primer extension, and set the stage for further structural dissection and optimization of the RNA copying process.
How do blind people represent rainbows? Disentangling components of conceptual representations
Authors: Striem-Amit Ella , Wang Xiaoying , Bi Yanchao , Caramazza Alfonso 
Published: March 2018

AbstractHow do we represent information that has no sensory features? How are abstract concepts like “freedom”, devoid of external perceptible referents, represented in the brain? To address the role of sensory information in the neural representation of concepts, we investigated how people born blind process concepts whose referents are imperceptible to them because of their visual nature (e.g. “rainbow”, or “red”). We find that the left dorsal anterior temporal lobe (ATL) shows preference both to typical abstract concepts (“freedom”) and to concepts whose referents are not sensorially-available to the blind (“rainbow”), as compared to partially sensorially-perceptible referents (e.g. “rain”). Activation pattern similarity in dorsal ATL is related to the sensorial-accessibility ratings of the concepts in the blind. Parts of inferior-lateral aspects of ATL and the temporal pole responded preferentially to abstract concepts devoid of any external referents (“freedom”) relative to imperceptible objects, in effect distinguishing between object and non-object concepts. The medial ATL showed a preference for concrete concepts (“cup”), along with a preference for partly perceptible items to the blind (“rain”, as compared with “rainbow”), indicating this region’s role in representing concepts with sensory referents beyond vision. The findings point to a new division of labor among medial, dorsal and lateral aspects of ATL in representing different properties of object and non-object concepts.
An aged human heart tissue model showing age-related molecular and functional deterioration resembling the native heart
Authors: Acun Aylin , Nguyen Trung Dung , Zorlutuna Pinar 
Published: March 2018

AbstractDeaths attributed to ischemic heart disease increased by 41.7% from 1990 to 2013. This is primarily due to an increase in the aged population, however, research on cardiovascular disease (CVD) has been overlooking aging, a well-documented contributor to CVD. The field heavily depends on the use of young animals due to lower costs and ready availability, despite the prominent differences between young and aged heart structure and function. Here we present the first human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (iCM)-based, in vitro aged myocardial tissue model as an alternative research platform. Within 4 months, iCMs go through accelerated senescence and show cellular characteristics of aging. Furthermore, the model tissues fabricated using these aged iCMs, with stiffness resembling that of aged human heart, show functional and pharmacological deterioration specific to aged myocardium. Our novel tissue model with age-appropriate physiology and pathology presents a promising new platform for investigating CVD or other age-related diseases.