bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coding and non-coding RNA dysregulation in bipolar disorder
Authors: Luykx Jurjen J. , Giuliani F. , Giuliani G. , Veldink J.H. 
Published: March 2018

AbstractThe molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. We found twenty genes, some of which not previously implicated in BPD, differentially expressed. PCR validation and replication confirmed the implication of these DE genes. Functional analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, we detected an overall increased number of alternative splicing events in BPD, as well as an increase in the number of genes carrying alternative splicing events. Finally, we report altered levels of two circular transcripts, cNEBL and cEPHA3. In conclusion, our non-coding RNA findings demonstrate that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.
A fungal ribonuclease-like effector protein inhibits plant host ribosomal RNA degradation
Authors: Pennington Helen G. , Jones Rhian , Kwon Seomun , Bonciani Giulia , Thieron Hannah , Chandler Thomas , Luong Peggy , Morgan Sian , Przydacz Michal , Bozkurt Tolga , Bowden Sarah , Craze Melanie , Wallington Emma , Garnett James , Kwaaitaal Mark , Panstruga Ralph , Cota Ernesto , Spanu Pietro D. 
Published: March 2018

ABSTRACTThe biotrophic fungal pathogenBlumeria graminiscauses the powdery mildew disease of cereals and grasses. Proteins with a predicted ribonuclease (RNase)-like fold (termed RALPHs) comprise the largest set of secreted effector candidates within theB. graminisf. sp.hordeigenome. Their exceptional abundance suggests they play crucial functions during pathogenesis. We show that transgenic expression of RALPH CSEP0064/BEC1054 increases susceptibility to infection in monocotyledenous and dicotyledonous plants. CSEP0064/BEC1054 interactsin plantawith five host proteins: two translation elongation factors (eEF1α and eEF1γ), two pathogenesis-related proteins (PR5 and PR10) and a glutathione-S-transferase. We present the first crystal structure of a RALPH, CSEP0064/BEC1054, demonstrating it has an RNase-like fold. The protein interacts with total RNA and weakly with DNA. Methyl jasmonate levels modulate susceptibility to aniline-induced host RNA fragmentation.In plantaexpression of CSEP0064/BEC1054 reduces the formation of this RNA fragment. We propose that CSEP0064/BEC1054 is a pseudoenzyme that binds to host ribosomes, thereby inhibiting the action of plant ribosome-inactivating proteins that would otherwise lead to host cell death, an unviable interaction and demise of the fungus.
Hippocampal signature of associative memory measured by chronic ambulatory intracranial EEG
Authors: Henin Simon , Shankar Anita , Hasulak Nicolas , Friedman Daniel , Dugan Patricia , Melloni Lucia , Flinker Adeen , Sarac Cansu , Fang May , Doyle Werner , Tcheng Thomas , Devinsky Orrin , Davachi Lila , Liu Anli 
Published: March 2018

ABSTRACTSome patients with medically refractory focal epilepsy are chronically implanted with a brain-responsive neurostimulation device (the RNS® System), permitting neurophysiological measurements at millisecond resolution. This clinical device can be adapted to measure hippocampal dynamics time-locked to cognitive tasks. We illustrate the technique with a proof of concept in three patients previously implanted with the RNS System as they engage in an associative memory task, measured months apart. Hippocampal activity measured in successful encoding in RNS System patients mirrors that in surgical patients during intracranial electroencephalography (iEEG), suggesting that chronic iEEG allows sensitive measurements of hippocampal physiology over prolonged timescales.
Age dependence of systemic bone loss and recovery following femur fracture in mice
Authors: Emami Armaun J. , Toupadakis Chrisoula A. , Telek Stephanie M. , Fyhrie David P. , Yellowley Clare E. , Christiansen Blaine A. 
Published: March 2018

AbstractThe most reliable predictor of future fracture risk is a previous fracture of any kind. The etiology of this increased fracture risk is not fully known, but it is possible that fracture initiates systemic bone loss leading to greater fracture risk at all skeletal sites. In this study we investigated systemic bone loss and recovery following femoral fracture in young (3 month old) and middle-aged (12 month old) mice. Transverse femur fractures were created using a controlled impact, and whole-body bone mineral density (BMD), trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, mouse voluntary movement, and systemic inflammation were quantified at multiple time points post-fracture. We found that fracture led to decreased whole-body BMD in both young and middle-aged mice 2 weeks post-fracture; this bone loss was recovered by 6 weeks in young, but not middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured mice relative to control mice 2 weeks post-fracture (−11% for young mice, −18% for middle-aged mice); this bone loss was fully recovered by 6 weeks post-fracture in young mice. At 3 days post-fracture we observed significant increases in serum levels of interleukin-6 and significant decreases in voluntary movement in fractured mice compared to control mice, with considerably greater changes in middle-aged mice than in young mice. At this time point we also observed increased osteoclast number on L5 vertebral body trabecular bone of fractured mice compared to control mice. These data show that systemic bone loss occurs after fracture in both young and middle-aged mice, and recovery from this bone loss may vary with age. This systemic response could contribute to increased future fracture risk following fracture, and these data may inform clinical treatment of fractures with respect to improving long-term skeletal health.
Cryptic selection forces and dynamic heritability in generalized phenotypic evolution
Authors: Gilpin William , Feldman Marcus W. 
Published: March 2018

AbstractIndividuals with different phenotypes can have widely-varying responses to natural selection, yet many classical approaches to evolutionary dynamics emphasize how a population’s average phenotype increases in fitness over time. However, recent experimental results have produced examples of populations that have multiple fitness peaks, or that experience frequency-dependence that affects the direction and strength of selection on certain individuals. Here, we extend classical fitness gradient formulations of natural selection in order to describe the dynamics of a phenotype distribution in terms of its moments—such as the mean, variance, skewness, etc. The number of governing equations in our model can be adjusted in order to capture different degrees of detail about the population. We compare our simplified model to direct Wright-Fisher simulations of evolution in several canonical fitness landscapes, we find that our model provides a low-dimensional description of complex dynamics not typically explained by classical theory, such as cryptic selection forces due to selection on trait ranges, time-variation of the heritability, and nonlinear responses to stabilizing or disruptive selection due to asymmetric trait distributions. In addition to providing a framework for extending general understanding of common qualitative concepts in phenotypic evolution—such as fitness gradients, selection pressures, and heritability—our approach has practical importance for studying evolution in contexts in which genetic analysis is infeasible.
Bayesian Inference for a Generative Model of Transcriptome Profiles from Single-cell RNA Sequencing
Authors: Lopez Romain , Regier Jeffrey , Cole Michael , Jordan Michael , Yosef Nir 
Published: March 2018

AbstractTranscriptome profiles of individual cells reflect true and often unexplored biological diversity, but are also affected by noise of biological and technical nature. This raises the need to explicitly model the resulting uncertainty and take it into account in any downstream analysis, such as dimensionality reduction, clustering, and differential expression. Here, we introduce Single-cell Variational Inference (scVI), a scalable framework for probabilistic representation and analysis of gene expression in single cells. Our model uses variational inference and stochastic optimization of deep neural networks to approximate the parameters that govern the distribution of expression values of each gene in every cell, using a non-linear mapping between the observations and a low-dimensional latent space.By doing so, scVI pools information between similar cells or genes while taking nuisance factors of variation such as batch effects and limited sensitivity into account. To evaluate scVI, we conducted a comprehensive comparative analysis to existing methods for distributional modeling and dimensionality reduction, all of which rely on generalized linear models. We first show that scVI scales to over one million cells, whereas competing algorithms can process at most tens of thousands of cells. Next, we show that scVI fits unseen data more closely and can impute missing data more accurately, both indicative of a better generalization capacity. We then utilize scVI to conduct a set of fundamental analysis tasks – including batch correction, visualization, clustering and differential expression – and demonstrate its accuracy in comparison to the state-of-the-art tools in each task. scVI is publicly available, and can be readily used as a principled and inclusive solution for multiple tasks of single-cell RNA sequencing data analysis.
Analysis of genome-wide differentiation between native and introduced populations of the cupped oystersCrassostrea gigasandCrassostrea angulata
Authors: Gagnaire Pierre-Alexandre , Lamy Jean-Baptiste , Cornette Florence , Heurtebise Serge , Dégremont Lionel , Flahauw Emilie , Boudry Pierre , Bierne Nicolas , Lapègue Sylvie 
Published: March 2018

AbstractThe Pacific cupped oyster is genetically subdivided into two sister taxa,Crassostrea gigasandC. angulata, which are in contact in the north-western Pacific. The nature and origin of their genetic and taxonomic differentiation remains controversial due the lack of known reproductive barriers and morphologic similarity. In particular, whether ecological and/or intrinsic isolating mechanisms participate to species divergence remains unknown. The recent co-introduction of both taxa into Europe offers a unique opportunity to test how genetic differentiation maintains under new environmental and demographic conditions. We generated a pseudo-chromosome assembly of the Pacific oyster genome using a combination of BAC-end sequencing and scaffold anchoring to a new high-density linkage map. We characterized genome-wide differentiation betweenC. angulataandC. gigasin both their native and introduced ranges, and showed that gene flow between species has been facilitated by their recent co-introductions in Europe. Nevertheless, patterns of genomic divergence between species remain highly similar in Asia and Europe, suggesting that the environmental transition caused by the co-introduction of the two species did not affect the genomic architecture of their partial reproductive isolation. Increased genetic differentiation was preferentially found in regions of low recombination. Using historical demographic inference, we show that the heterogeneity of differentiation across the genome is well explained by a scenario whereby recent gene flow has eroded past differentiation at different rates across the genome after a period of geographical isolation. Our results thus support the view that low-recombining regions help in maintaining intrinsic genetic differences between the two species.
An ultra-dense haploid genetic map for evaluating the highly fragmented genome assembly of Norway spruce(Picea abies)
Authors: Bernhardsson Carolina , Vidalis Amaryllis , Wang Xi , Scofield Douglas G. , Schiffthaler Bastian , Basion John , Street Nathaniel R. , García-Gil M. Rosario , Ingvarsson Pär K. 
Published: March 2018

AbstractNorway spruce (Picea abies(L.) Karst.) is a conifer species of substanital economic and ecological importance. In common with most conifers, theP. abiesgenome is very large (∼20 Gbp) and contains a high fraction of repetitive DNA. The currentP. abiesgenome assembly (v1.0) covers approximately 60% of the total genome size but is highly fragmented, consisting of >10 million scaffolds. The genome annotation contains 66,632 gene models that are at least partially validated (www.congenie.org), however, the fragmented nature of the assembly means that there is currently little information available on how these genes are physically distributed over the 12P. abieschromosomes. By creating an ultra-dense genetic linkage map, we anchored and ordered scaffolds into linkage groups, which complements the fine-scale information available in assembly contigs. Our ultra-dense haploid consensus genetic map consists of 21,056 markers derived from 14,336 scaffolds that contain 17,079 gene models (25.6% of the validated gene models) that we have anchored to the 12 linkage groups. We used data from three independent component maps, as well as comparisons with previously publishedPiceamaps to evaluate the accuracy and marker ordering of the linkage groups. We demonstrate that approximately 3.8% of the anchored scaffolds and 1.6% of the gene models covered by the consensus map have likely assembly errors as they contain genetic markers that map to different regions within or between linkage groups. We further evaluate the utility of the genetic map for the conifer research community by using an independent data set of unrelated individuals to assess genome-wide variation in genetic diversity using the genomic regions anchored to linkage groups. The results show that our map is sufficiently dense to enable detailed evolutionary analyses across theP. abiesgenome.
Stroke survivors show task-dependent modulation of motor variability during bimanual coordination
Authors: Ranganathan Rajiv , Gebara Rani , Andary Michael , Sylvain Jim 
Published: March 2018

ABSTRACTStroke often results in hemiparesis, leaving one side of the body ‘affected’ relative to the other side. Prior research has shown that the affected arm has higher variability – however, the extent to which this variability can be modulated is unclear. Here we used a shared bimanual task to examine the degree to which participants could modulate the variability in the affected arm after stroke. Participants with chronic stroke (n = 11), and age-matched controls (n = 11) performed unimanual and bimanual reaching movements to move a cursor on a screen to different targets. In the unimanual condition, the cursor was controlled only by the movement of a single arm whereas in the bimanual condition, the cursor position was “shared” between the two arms by using a weighted average of the two hand positions. Unknown to the participants, we altered the weightings of the affected and unaffected arms to cursor motion and examined how the movement variability on each arm changed depending on its contribution to the task. Results showed that stroke survivors had higher movement variability on the affected arm – however, like age-matched controls, they were able to modulate the variability in both the affected and unaffected arms according to the weighting condition. Specifically, as the weighting on a particular arm increased (i.e. it became more important to the task), the movement variability decreased. These results show that stroke survivors are capable of modulating variability depending on the task context, and this feature may potentially be exploited for rehabilitation paradigms
HIV-1 Env gp41 Transmembrane Domain Dynamics are Modulated by Lipid, Water, and Ion Interactions
Authors: Hollingsworth L.R. , Lemkul J.A. , Bevan D.R. , Brown A.M. 
Published: March 2018

AbstractThe gp41 transmembrane domain (TMD) of the envelope glycoprotein (Env) of the human immunodeficiency virus (HIV) modulates the conformation of the viral envelope spike, the only druggable target on the surface of the virion. Understanding of TMD dynamics is needed to better probe and target Env with small molecule and antibody therapies. However, little is known about TMD dynamics due to difficulties in describing native membrane properties. Here, we performed atomistic molecular dynamics simulations of a trimeric, prefusion TMD in a model, asymmetric viral membrane that mimics the native viral envelope. We found that water and chloride ions permeated the membrane and interacted with the highly conserved arginine bundle, (R696)3, at the center of the membrane and influenced TMD stability by creating a network of hydrogen bonds and electrostatic interactions. We propose that this (R696)3- water - anion network plays an important role in viral fusion with the host cell by modulating protein conformational changes within the membrane. Additionally, R683 and R707 at the exofacial and cytofacial membrane-water interfaces, respectively, are anchored in the lipid headgroup region and serve as a junction point for stabilization of the termini. The membrane thins as a result of the tilting of the TMD trimer, with nearby lipids increasing in volume, leading to an entropic driving force for TMD conformational change. These results provide additional detail and perspective on the influence of certain lipid types on TMD dynamics and rationale for targeting key residues of the TMD for therapeutic design. These insights into the molecular details of TMD membrane anchoring will build towards a greater understanding of dynamics that lead to viral fusion with the host cell.
ImageJ Macro for Counting Stationary vs. Moving Items in Videos
Authors: Douglas T. , Davalos R. 
Published: March 2018

ABSTRACTIn microfluidic devices, it is often necessary to determine whether cells or particles are stationary or moving. Here we outline the development of an ImageJ macro that can be used to analyze a video of moving, fluorescently labeled particles or cells, and determine which objects are stationary and which objects are moving at each point in time, providing information on the percentage of cells moving as well as their median radius.
Estimating RNA structure chemical probing reactivities from reverse transcriptase stops and mutations
Authors: Yu Angela M , Evans Molly E. , Lucks Julius B. 
Published: March 2018

ABSTRACTChemical probing experiments interrogate RNA structures by creating covalent adducts on RNA molecules in structure-dependent patterns. Adduct positions are then detected through conversion of the modified RNAs into complementary DNA (cDNA) by reverse transcription (RT) as either stops (RT-stops) or mutations (RT-mutations). Statistical analysis of the frequencies of RT-stops and RT-mutations can then be used to estimate a measure of chemical probing reactivity at each nucleotide of an RNA, which reveals properties of the underlying RNA structure. Inspired by recent work that showed that different reverse transcriptase enzymes show distinct biases for detecting adducts as either RT-stops or RT-mutations, here we use a statistical modeling framework to derive an equation for chemical probing reactivity using experimental signatures from both RT-stops and RT-mutations within a single experiment. The resulting formula intuitively matches the expected result from considering reactivity to be defined as the fraction of adduct observed at each position in an RNA at the end of a chemical probing experiment. We discuss assumptions and implementation of the model, as well as ways in which the model may be experimentally validated.
Fatal Poisoning with Both Dichlorvos and Phenthoate,
Authors: Nara Akina , Yamada Chiho , Kodama Takanori , Saka Kanju , Takagi Tetsuya 
Published: March 2018

AbstractOrganophosphates are widely used as pesticides. However, organophosphates are occasionally orally ingested to commit suicide. In this case, a man in his late 80s committed suicide by ingesting both dichlorvos and phenthoate. Autopsy findings revealed a characteristic volatile odor from his mouth, stomach, lungs, liver, and kidneys. The esophageal mucosa was denatured and had lost elasticity. Serum cholinesterase activity was 9 IU/L. Toxicological analyses performed using high‐performance liquid chromatography–tandem mass spectrometry revealed that dichlorvos concentrations in the left and right cardiac blood samples were 11.6 and 4.6 μg/mL, respectively. Phenthoate concentrations in the left and right cardiac blood samples were 5.8 and 0.51 μg/mL, respectively. The total amounts of dichlorvos and phenthoate in the stomach were 7.35 and 4.55 g, respectively. The case history, autopsy findings, and toxicological analyses indicated that the cause of death was acute fatal poisoning after oral ingestion of both dichlorvos and phenthoate.
Optimization of Sample Preparation processes of Bone Material for Raman Spectroscopy
Authors: Chikhani Madelen , Wuhrer Richard , Green Hayley 
Published: March 2018

AbstractRaman spectroscopy has recently been investigated for use in the calculation of postmortem interval from skeletal material. The fluorescence generated by samples, which affects the interpretation of Raman data, is a major limitation. This study compares the effectiveness of two sample preparation techniques, chemical bleaching and scraping, in the reduction of fluorescence from bone samples during testing with Raman spectroscopy. Visual assessment of Raman spectra obtained at 1064 nm excitation following the preparation protocols indicates an overall reduction in fluorescence. Results demonstrate that scraping is more effective at resolving fluorescence than chemical bleaching. The scraping of skeletonized remains prior to Raman analysis is a less destructive method and allows for the preservation of a bone sample in a state closest to its original form, which is beneficial in forensic investigations. It is recommended that bone scraping supersedes chemical bleaching as the preferred method for sample preparation prior to Raman spectroscopy.