bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental Effects of the Pesticide Imidacloprid on Zebrafish Body Length and Mortality
Authors: Krishnan Akshay , Clyburn Christin , Newcombe Patrick 
Published: August 2018

AbstractThe pesticide imidacloprid, a Neonicotinoid, is widely used and commercially available. Neonicotinoids are antagonists at nicotinic acetylcholine receptors, which can cause neurobehavioral effects in developing organisms. While the effects of other insecticides such as Malathion and Fipronil on zebrafishDanio reriodevelopment have been studied, few studies describe the morphological effects of imidacloprid during zebrafish development. To test the hypothesis that imidacloprid concentration positively correlates to increased mortality and decreased body length, we exposed zebrafish to imidacloprid for five days post fertilization. Body length and embryo mortality were recorded at 1, 2, 3, 4, and 5 days post fertilization in 0 ug/L, 100 ug/L, 1,000 ug/L, and 10,000 ug/L imidacloprid concentrations. These concentrations were chosen to mimic levels that could be reached in the environment especially soon after application. Our results demonstrate statistically increased embryo mortality, with a f crit value of 3.193 and a f value of 3.098 from an ANOVA test, and impaired body length with a dose dependent correlation to the concentration of imidacloprid and a P value of less than 0.01 from a T test. Given the pesticide’s high prevalence, future studies should be considered to determine if this effect may impact livestock and human development.
Whole-neuron synaptic mapping reveals local balance between excitatory and inhibitory synapse organization
Authors: Iascone Daniel Maxim , Li Yujie , Sümbül Uygar , Doron Michael , Chen Hanbo , Andreu Valentine , Goudy Finola , Segev Idan , Peng Hanchuan , Polleux Franck 
Published: August 2018

SUMMARYThe balance between excitatory and inhibitory (E and I) synaptic inputs is thought to be critical for information processing in neural circuits. However, little is known about the principles of spatial organization of E and I synapses across the entire dendritic tree of mammalian neurons. We developed a new, open-source, reconstruction platform for mapping the size and spatial distribution of E and I synapses received by individual, genetically-labeled, layer 2/3 cortical pyramidal neurons (PNs) in vivo. We mapped over 90,000 E and I synapses across twelve L2/3 PNs and uncovered structured organization of E and I synapses across dendritic domains as well as within individual dendritic segments in these cells. Despite significant, domain-specific, variations in the absolute density of E and I synapses, their ratio is strikingly balanced locally across dendritic segments. Computational modeling indicates that this spatially-precise E/I balance dampens dendritic voltage fluctuations and strongly impacts neuronal firing output.
A Proof-of-Principle of Nanoscale Optogenetics
Authors: Stahlberg Markus A. , Ramakrishnan Charu , Willig Katrin I. , Boyden Edward S. , Deisseroth Karl , Dean Camin 
Published: August 2018

AbstractOptogenetics has revolutionized the study of circuit function in the brain, by allowing activation of specific ensembles of neurons by light. However, this technique has not yet been exploited extensively at the subcellular level. Here we propose a novel focal stimulation approach using STED/RESOLFT-like illumination, whereby switchable light-gated channels are focally activated by a laser beam of one wavelength and deactivated by an overlapping donut-shaped beam of a different wavelength, confining activation to a center focal region. We demonstrate the utility of current optogenetic tools to achieve highly focal depolarization using this method and further examine a proof-of-principle of nanoscale optogenetic activation using an initial macroscale approach. When employed at the nanoscale, this approach will allow unprecedented optogenetic control of nanodomains within cells.
Molecular structure and function of myelin protein P0 in membrane stacking
Authors: Raasakka Arne , Ruskamo Salla , Kowal Julia , Han Huijong , Baumann Anne , Myllykoski Matti , Fasano Anna , Rossano Rocco , Riccio Paolo , Bürck Jochen , Ulrich Anne S. , Stahlberg Henning , Kursula Petri 
Published: August 2018

AbstractCompact myelin forms the basis of nerve insulation essential for higher vertebrates. Dozens of myelin membrane bilayers undergo tight stacking, and in the peripheral nervous system, this is partially enabled by myelin protein zero (P0). Consisting of an immunoglobulin (Ig)-like extracellular domain, a single transmembrane helix, and a cytoplasmic extension (P0ct), P0 harbours an important task in ensuring the integrity of compact myelin in the extracellular compartment, referred to as the intraperiod line. Several disease mutations resulting in peripheral neuropathies have been identified for P0, reflecting its physiological importance, but the arrangement of P0 within the myelin ultrastructure remains obscure. We performed a biophysical characterization of recombinant P0ct. P0ct contributes to the binding affinity between apposed cytoplasmic myelin membrane leaflets, which not only results in fluidity changes of the bilayers themselves, but also potentially involves the rearrangement of the Ig-like domains in a manner that stabilizes the intraperiod line. Transmission electron cryomicroscopy of native full-length P0 showed that P0 stacks lipid membranes by forming antiparallel dimers between the extracellular Ig-like domains. The zipper-like arrangement of the P0 extracellular domains between two membranes explains the double structure of the myelin intraperiod line. Our results contribute to the understanding of PNS myelin, the role of P0 therein, and the underlying molecular foundation of compact myelin stability in health and disease.
Opposing effects of prostaglandin receptor EP2 signaling in mouse immune cells and neurons after status epilepticus
Authors: Varvel Nicholas H. , Chen Di , Biegel Ariel , Dingledine Raymond 
Published: August 2018

AbstractA multidimensional inflammatory response ensues after status epilepticus (SE), driven partly by cyclooxygenase-2 mediated activation of prostaglandin EP2 receptors. Here we identify those effects of EP2 antagonism that are reproduced by conditional ablation of EP2 receptors in immune myeloid cells and forebrain neurons. Removal of myeloid cell EP2 dampened induction of hippocampal IL-6, prevented erosion of the blood-brain barrier, accelerated weight regain, and relieved ptosis following SE. Elimination of EP2 receptor from neurons enhanced neuronal injury, elevated hippocampal induction of the pro-inflammatory cytokines, TNFα and Ccl2, promoted deterioration of the blood-brain barrier, delayed weight recovery, and worsened animal posture and activity. Taken together these data highlight the complexities in neuroinflammatory signaling, wherein activation of EP2 receptors in innate immune cells is deleterious but neuronal EP2 signaling is protective. Effective treatments targeting brain prostaglandin signaling pathways should be cell targeted to be optimally effective.Significance StatementSeizures reduce quality of life, promote the development of epilepsy, and can be fatal. We previously identified inflammation, via prostaglandin receptor EP2 activation, as a driver of undesirable seizure-induced effects. However, the relevant EP2-expressing cell types remain unclear. We identify innate immune cells as a driver of the EP2-related negative consequences of seizures, whereas neuronal EP2 signaling is protective. Genetic removal of EP2 from immune cells was beneficial, accelerating weight gain and limiting behavioral deficits. Elimination of EP2 from neurons was harmful, worsening behavioral deficits and promoting neuronal damage. These findings enhance our understanding of the complex inflammatory processes engaged after seizures and will assist in the development of beneficial therapies to enhance quality of life in individuals susceptible to seizures.
Single cell RNA-seq study of wild type and Hox9,10,11 mutant developing uterus
Authors: Mucenski Michael L. , Mahoney Robert , Adam Mike , Potter Andrew S. , Potter S. Steven 
Published: August 2018

AbstractThe uterus is a remarkable organ that must guard against infections while maintaining the ability to support growth of a fetus without rejection. TheHoxa10andHoxa11genes have previously been shown to play essential roles in uterus development and function. In this report we show that theHoxc9,10,11genes play a redundant role in the formation of uterine glands. In addition, we use single cell RNA-seq to create a high resolution gene expression atlas of the developing wild type mouse uterus. Cell types and subtypes are defined, for example dividing endothelial cells into arterial, venous, capillary, and lymphatic, while epithelial cells separate into luminal and glandular subtypes. Further, a surprising heterogeneity of stromal and myocyte cell types are identified. Transcription factor codes and ligand/receptor interactions are characterized. We also used single cell RNA-seq to globally define the altered gene expression patterns in all developing uterus cell types for two Hox mutants, with 8 or 9 mutant Hox genes. The mutants show a striking disruption of Wnt signaling as well as the Cxcl12/Cxcr4 ligand/receptor axis.Summary statementA single cell RNA-seq study of the developing mouse uterus defines cellular heterogeneities, lineage specific gene expression programs and perturbed pathways in Hox9,10,11 mutants.
Transcriptome Analysis of Distinct Cold Tolerance Strategies in the Rubber Tree (Hevea brasiliensis)
Authors: Mantello Camila Campos , Boatwright Lucas , da Silva Carla Cristina , Scaloppi Erivaldo Jose , Souza Gonçalves Paulo de , Barbazuk W. Brad , de Souza Anete Pereira 
Published: August 2018

AbstractNatural rubber is an indispensable commodity used in approximately 40,000 products and is fundamental to the tire industry. Among the species that produce latex, the rubber tree [Hevea brasiliensis (Willd. ex Adr. de Juss.) Muell-Arg.], a species native to the Amazon rainforest, is the major producer of latex used worldwide. The Amazon Basin presents optimal conditions for rubber tree growth, but the occurrence of South American leaf blight, which is caused by the fungus Microcyclus ulei (P. Henn) v. Arx, limits rubber tree production. Currently, rubber tree plantations are located in scape regions that exhibit suboptimal conditions such as high winds and cold temperatures. Rubber tree breeding programs aim to identify clones that are adapted to these stress conditions. However, rubber tree breeding is time-consuming, taking more than 20 years to develop a new variety. It is also expensive and requires large field areas. Thus, genetic studies could optimize field evaluations, thereby reducing the time and area required for these experiments. Transcriptome sequencing using next-generation sequencing (RNA-seq) is a powerful tool to identify a full set of transcripts and for evaluating gene expression in model and non-model species. In this study, we constructed a comprehensive transcriptome to evaluate the cold response strategies of the RRIM600 (cold-resistant) and GT1 (cold-tolerant) genotypes. Furthermore, we identified putative microsatellite (SSR) and single-nucleotide polymorphism (SNP) markers. Alternative splicing, which is an important mechanism for plant adaptation under abiotic stress, was further identified, providing an important database for further studies of cold tolerance.
Morphogenetic processes as data: Quantitative structure in theDrosophilaeye imaginal disc
Authors: Alicea Bradly , Portegys Thomas E. , Gordon Diana , Gordon Richard 
Published: August 2018

AbstractWe can improve our understanding of biological processes through the use of computational and mathematical modeling. One such morphogenetic process (ommatidia formation in theDrosophilaeye imaginal disc) provides us with an opportunity to demonstrate the power of this approach. We use a high-resolution image that catches the spatially- and temporally-dependent process of ommatidia formation in the act. This image is converted to quantitative measures and models that provide us with new information about the dynamics and geometry of this process. We approach this by addressing three computational hypotheses, and provide a publicly-available repository containing data and images for further analysis. Potential spatial patterns in the morphogenetic furrow and ommatidia are summarized, while the ommatidia cells are projected to a spherical map in order to identify higher-level spatiotemporal features. In the conclusion, we discuss the implications of our approach and findings for developmental complexity and biological theory.
Altitudinal range-size distribution of breeding birds and environmental factors for the determination of species richness: An empirical test of altitudinal Rapoport’s rule and rescue effect on a local scale
Authors: Kim Jin-Yong , Seo Changwan , Hong Seungbum , Lee Sanghoon , Eo Soo Hyung 
Published: August 2018

AbstractRange-size distributions are important for understanding species richness patterns and led to the development of the controversial Rapoport’s rule and Rapoport-rescue effect. This study aimed to understand the relationship between species richness and range-size distribution in relation to environmental factors. The present study tested the following: (1) altitudinal Rapoport’s rule, (2) climatic and ambient energy hypotheses, (3) non-directional rescue effect, and (4) effect of environmental factors on range-size group. Altitudinal species range-size distribution increased with increasing altitude and showed a negative relationship with climatic variables and habitat heterogeneity, and a positive relationship with primary productivity. These results support the altitudinal Rapoport’s rule and climatic hypothesis; however, they do not fully support the ambient energy hypothesis. Results from testing the non-directional rescue effect showed that the inflow intensity of species from both directions (high and low elevations) affected species richness. And we found that the 2nd and 3rd quartile species distribution were the main cause of a mid-peak of species richness and the non-directional rescue effect. Additionally, the 2nd quartile species richness was highly related to minimum temperature and possessed thermal specialist species features, and the 3rd quartile species richness was highly related to habitat heterogeneity and primary productivity. Although altitudinal range-size distribution results were similar to the altitudinal Rapoport’s rule, the mid-peak pattern of species richness could not be explained by the Rapoport’s-rescue effect; however, the non-directional rescue effect could explain a mid-peak pattern of species richness.
Nucleosome dynamics of human iPSC during the early stages of neurodevelopment
Authors: Harwood Janet C , Kent Nicholas A , Allen Nicholas D , Harwood Adrian J 
Published: August 2018

AbstractRegulation of nucleosome positioning is important for neurodevelopment, and mutation of genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. Unicellular organisms possess arrays of highly positioned nucleosomes within their chromatin, occupying up to 80% of their genomes. These span gene-coding and regulatory regions, and can be associated with local changes of gene transcription. In the much larger genome of human cells, the roles of nucleosome positioning are less clear, and this raises questions of how nucleosome dynamics interfaces with human neurodevelopment.We have generated genome-wide nucleosome maps from an undifferentiated human induced pluripotent stem cell (hiPSC) line and after its differentiation to the neuronal progenitor cell (NPC) stage. We found that approximately 3% of nucleosomes are highly positioned in NPC. In contrast, there are 8-fold less positioned nucleosomes in pluripotent cells, with the majority arisingde novoor relocating during cell differentiation. Positioned nucleosomes do not directly correlate with active chromatin or gene transcription, such as marking Transcriptional Start Sites (TSS). Unexpectedly, we find a small population of nucleosomes that remain positioned after differentiation, occupying similar positions in pluripotent and NPC cells. They flank the binding sites of the key gene regulators NRSF/REST and CTCF, but remain in place whether or not their regulatory complexes are present. Together, these results present an alternative view in human cells, where positioned nucleosomes are sparse and dynamic, but act to alter gene expression at a distance via structural conformation at sites of chromatin regulation, not local changes in gene organisation.
Epigenomic and functional characterization of a core DNA methyltransferase in the human pathogenClostridium difficile
Authors: Oliveira Pedro H. , Ribis John W. , Garrett Elizabeth M. , Trzilova Dominika , Kim Alex , Sekulovic Ognjen , Mead Edward A. , Pak Theodore , Zhu Shijia , Deikus Gintaras , Touchon Marie , Beckford Colleen , Zeitouni Nathalie E. , Altman Deena , Webster Elizabeth , Oussenko Irina , Bunyavanich Supinda , Aggarwal Aneel K. , Bashir Ali , Patel Gopi , Hamula Camille , Huprikar Shirish , Schadt Eric E. , Sebra Robert , van Bakel Harm , Kasarskis Andrew , Tamayo Rita , Shen Aimee , Fang Gang 
Published: August 2018

AbstractClostridioides difficileis a leading cause of health care-associated infections. Although significant progress has been made in the understanding of its genome, the epigenome ofC. difficileand its functional impact has not been systematically explored. Here, we performed the first comprehensive DNA methylome analysis ofC. difficileusing 36 human isolates and observed great epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity whose corresponding gene is highly conserved across our dataset and in all ~300 globalC. difficilegenomes examined. Inactivation of the methyltransferase gene negatively impacted sporulation, a key step inC. difficiledisease transmission, consistently supported by multi-omics data, genetic experiments, and a mouse colonization model. Further experimental and transcriptomic analysis also suggested that epigenetic regulation is associated with cell length, biofilm formation, and host colonization. These findings open up a new epigenetic dimension to characterize medically relevant biological processes in this critical pathogen. This work also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomics studies.
Thalamo-cortical interactions define functional dissociations across the macaque attention network
Authors: Fiebelkorn Ian C. , Pinsk Mark A. , Kastner Sabine 
Published: August 2018

ABSTRACTSpatial attention is discontinuous, sampling behaviorally relevant locations in theta-rhythmic cycles (3–6 Hz). Underlying this rhythmic sampling are intrinsic theta oscillations in frontal and parietal cortices that provide a clocking mechanism for two alternating attentional states that are associated with either engagement at the presently attended location (and enhanced perceptual sensitivity) or disengagement (and diminished perceptual sensitivity). It has remained unclear, however, how these theta-dependent states are coordinated across the large-scale network that directs spatial attention. The pulvinar is a candidate for such coordination, having been previously shown to regulate cortical activity. We therefore examined pulvino-cortical interactions during theta-rhythmic sampling by simultaneously recording from FEF, LIP, and the pulvinar. Neural activity propagated from (i) pulvinar to cortex during periods of engagement and (ii) from cortex to pulvinar during periods of disengagement. A rhythmic reweighting of pulvino-cortical interactions thus defines functional dissociations in the macaque attention network.
Long-read Sequencing Uncovers a Complex Transcriptome Topology in Varicella Zoster Virus
Authors: Prazsák István , Moldován Norbert , Tombácz Dóra , Megyeri Klára , Szűcs Attila , Csabai Zsolt , Boldogkői Zsolt 
Published: August 2018

AbstractBackgroundVaricella zoster virus (VZV) is a human pathogenic alphaherpesvirus harboring a relatively large DNA molecule. The VZV transcriptome has already been analyzed by microarray and short-read sequencing analyses. However, both approaches have substantial limitations when used for structural characterization of transcript isoforms, even if supplemented with primer extension or other techniques. Among others, they are inefficient in distinguishing between embedded RNA molecules, transcript isoforms, including splice and length variants, as well as between alternative polycistronic transcripts. It has been demonstrated in several studies that long-read sequencing is able to circumvent these problems.ResultsIn this work, we report the analysis of VZV lytic transcriptome using the Oxford Nanopore Technologies sequencing platform. These investigations have led to the identification of 114 novel transcripts, including mRNAs, non-coding RNAs, polycistronic RNAs and complex transcripts, as well as 10 novel spliced transcripts and 27 novel transcription start site isoforms and transcription end site isoforms. A novel class of transcripts, the nroRNAs are described in this study. These transcripts are encoded by the genomic region located in close vicinity to the viral replication origin. We also show that the VZV latency transcript (VLT) exhibits a more complex structural variation than formerly believed. Additionally, we have detected RNA editing in a novel non-coding RNA molecule.ConclusionsOur investigations disclosed a composite transcriptomic architecture of VZV, including the discovery of novel RNA molecules and transcript isoforms, as well as a complex meshwork of transcriptional read-throughs and overlaps. The results represent a substantial advance in the annotation VZV transcriptome and in understanding the molecular biology of the herpesviruses in general.
Kinpute: Using identity by descent to improve genotype imputation
Authors: Abney Mark , El Sherbiny Aisha 
Published: August 2018

1AbstractMotivationGenotype imputation, though generally accurate, often results in many genotypes being poorly imputed, particularly in studies where the individuals are not well represented by standard reference panels. When individuals in the study share regions of the genome identical by descent (IBD), it is possible to use this information in combination with a study specific reference panel (SSRP) to improve the imputation results. Kinpute uses IBD information—due to either recent, familial relatedness or distant, unknown ancestors— in conjunction with the output from linkage disequilibrium (LD) based imputation methods to compute more accurate genotype probabilities. Kinpute uses a novel method for IBD imputation, which works even in the absence of a pedigree, and results in substantially improved imputation quality.ResultsGiven initial estimates of average IBD between subjects in the study sample, Kinpute uses a novel algorithm to select an optimal set of individuals to sequence and use as an SSRP. Kinpute is designed to use as input both this SSRP and the genotype probabilities output from other LD based imputation software, and uses a new method to combine the LD imputed genotype probabilities with IBD configurations to substantially improve imputation. We tested Kinpute on a human population isolate where 98 individuals have been sequenced. In half of this sample, whose sequence data was masked, we used Impute2 to perform LD based imputation and Kinpute was used to obtain higher accuracy genotype probabilities. Measures of imputation accuracy improved significantly, particularly for those genotypes that Impute2 imputed with low certainty.AvailabilityKinpute is an open-source and freely available C++ software package that can be downloaded from https://github.com/markabney/Kinpute/releases.