bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of Multiple Sclerosis in Eastern Mediterranean Region (1990-2016): Findings From the 2016 Global Burden of Disease Study
Authors: Sahraian Mohammad Ali , Heydarpour Pouria , Moradi-Lakeh Maziar , Eskandarieh Sharareh , Fereshtehnejad Seyed-Mohammad , Vosughi Kia , Rahimi-Movaghar Vafa , Farzadfar Farshad , Malekzadeh Reza , Vos Theo , Feigin Valery , Naghavi Mohsen , Mokdad Ali H. 
Published: September 2019

AbstractBackgroundMultiple sclerosis (MS) is among the leading causes of disability in Young Adults worldwide. Current estimates of MS burden in Eastern Mediterranean Region (EMR) are necessary for planning effective interventions .To estimate Prevalence, incidence, mortality, years lived with disability (YLDs), years of life lost (YLLs) and disability-adjusted life-years (DALYs) in EMR by country age, and sex from 1990 to 2016.MethodsWe estimated regional and country-specific prevalence, incidence, mortality, DALYs, YLLs, and YLDs for MS. DALYs were computed as the sum of YLDs and YLLs.ResultsTotal DALYs in EMR countries was 12,810 in 1990 for males and increased to 36,391 in 2016 and from 18,962 to 53,851 for females. Lowest DALYs in both sexes were observed in Somalia (248) while the highest were in Iran (26,394). YLDs in males increased from 6,511 in 1990 to 19,515 in 2016, and in females from 12,247 to 33,937. The highest age-standardized prevalence, incidence, YLDs and DALYs were in Iran (72.11, 2.49, 18.03, and 32.5, respectively).ConclusionsOur findings provide valuable information to guide the development and implementation of measures to address the rising burden of MS and it consequences in the EMR countries.
Early vegetation recovery after the 2008-2009 explosive eruption of the Chaitén Volcano
Authors: Moreno-González Ricardo , Díaz Iván A. , Christie Duncan A. , Coopman Rafael E. , Lara Antonio 
Published: September 2019

AbstractIn May 2008, Chaitén volcano entered in eruptive process, one of the world largest eruptions in the last decades. The catastrophic event left different type of disturbance and caused diverse environmental damage distributed heterogeneously in the surrounding areas of the volcano. We went to the field to assess the early vegetation responses a year after the eruption, in September 2009. Particularly, we evaluated the lateral-blast disturbance zone. We distributed a set of plots in three disturbed sites, and one in an undisturbed site. In each of these sites, in a plot of 1000m2 we marked all stand tree, recording whether they were alive, resprouting or dead. Additionally, in each site 80 small-plots (~4m2) we tallied the plants regeneration, its coverage, and the log-volume. We described whether the plant regeneration was growing on mineral or organic substrate. In the blast-zone the eruption created a gradient of disturbance. Close to the crater we found high devastation marked by no surviving species, scarce standing-dead trees and logs, as well as no tree regeneration. On the other extreme of the disturbance gradient, the trees with damaged crown were resprouting, small-plants were regrowing and seedlings were more dispersed. The main regeneration strategy was the resprouting of trunks or buried roots, while few seedlings were observed in the small plots and elsewhere in disturbed areas. However, the assessment was too soon after the eruption and updated monitoring is required to confirm observed patterns. The main findings of this study are: i) a mosaic of pioneering-wind dispersed species, scattered survivors regrowing and spreading from biological legacies, and plant species dispersed by frugivorous birds, likely favored by the biological legacies; (ii) the early succession is influenced by the interaction of the species-specific life history, altitudinal gradient and the different intensity of disturbance.
Measuring stepwise binding of a thermally fluctuating particle to a cell membrane without labeling
Authors: Rohrbach A. , Meyer T. , Kress H. 
Published: September 2019

ABSTRACTThermal motions enable a particle to probe the optimal interaction state when binding to a cell membrane. However, especially on the scale of microseconds and nanometers, position and orientation fluctuations are difficult to observe with common measurement technologies. Here we show that it is possible to detect single binding events of IgG-coated polystyrene beads, which are held in an optical trap nearby the cell membrane of a macrophage. Changes in the spatial and temporal thermal fluctuations of the particle were measured interferometrically and no fluorophore labelling was required. We demonstrate both by Brownian dynamic simulations and by experiments that sequential step-wise increases in the force constant of the bond between a bead and a cell of typically 20 pN / µm are clearly detectable. In addition, this technique provides estimates about binding rates and diffusion constants of membrane receptors. The simple approach of thermal noise tracking points out new strategies in understanding interactions between cells and particles, which are relevant for a large variety of processes including phagocytosis, drug delivery or the effects of small microplastics and particulates on cells.SIGNIFICANCEInteractions of cells with nearby particles, e.g. bacteria, viruses or synthetic material, is a very fundamental and complex process, often deciding about the cellular fate. The investigation of binding processes between particle and cell is typically investigated by fluorescence techniques, where fluorophores often hinder the molecular interaction of specific binding partners. Therefore, label-free detection or imaging techniques are essential, which are hardly available especially for live cell investigations. Molecular binding is based on thermal position and orientation fluctuations of the binding partners to find the best interaction state. Here, we present a label-free measurement technique that allows us to detect multiple stepwise binding events of molecules on an optically trapped particle close to the cell membrane.
Reproducible and Transparent Research Practices in Published Neurology Research
Authors: Rauh Shelby , Torgerson Trevor , Johnson Austin L. , Pollard Jonathan , Tritz Daniel , Vassar Matt 
Published: September 2019

AbstractBackgroundThe objective of this study was to evaluate the nature and extent of reproducible and transparent research practices in neurology research.MethodsThe NLM catalog was used to identify MEDLINE-indexed neurology journals. A PubMed search of these journals was conducted to retrieve publications over a 5-year period from 2014 to 2018. A random sample of publications was extracted. Two authors conducted data extraction in a blinded, duplicate fashion using a pilot-tested Google form. This form prompted data extractors to determine whether publications provided access to items such as study materials, raw data, analysis scripts, and protocols. In addition, we determined if the publication was included in a replication study or systematic review, was preregistered, had a conflict of interest declaration, specified funding sources, and was open access.ResultsOur search identified 223,932 publications meeting the inclusion criteria, from which 300 were randomly sampled. Only 290 articles were accessible, yielding 202 publications with empirical data for analysis. Our results indicate that 8.99% provided access to materials, 9.41% provided access to raw data, 0.50% provided access to the analysis scripts, 0.99% linked the protocol, and 3.47% were preregistered. A third of sampled publications lacked funding or conflict of interest statements. No publications from our sample were included in replication studies, but a fifth were cited in a systematic review or meta-analysis.ConclusionsCurrent research in the field of neurology does not consistently provide information needed for reproducibility. The implications of poor research reporting can both affect patient care and increase research waste. Collaborative intervention by authors, peer reviewers, journals, and funding sources is needed to mitigate this problem.
Kinomorphs: Shape-shifting tissues for developmental engineering
Authors: Viola John M. , Porter Catherine M. , Gupta Ananya , Alibekova Mariia , Prahl Louis S. , Hughes Alex J. 
Published: September 2019

AbstractCurrent methods for building tissues usually start with a non-biological blueprint, or rely on self-organization, which does not extend to organ-scales. This has limited the construction of large tissues that simultaneously encode fine-scale cell organization. Here we bridge scales by mimicking developmental dynamics using “kinomorphs”, tissue scaffolds that undergo globally programmed shape and density changes to trigger local self-organization of cells in many locations at once. In this first report, we focus on mimicking the extracellular matrix (ECM) compaction and division into leaflets that occurs in kidney collecting duct development. We start by creating single-cell resolution cell patterns in ECM-mimetic hydrogels that are >10x larger than previously described, by leveraging photo-lithographic technology. These patterns are designed to mimic the branch geometry of the embryonic kidney collecting duct tree. We then predict the shape dynamics of kinomorphs driven by cell contractility-based compaction of the ECM using kinematic origami simulations. We show that these dynamics spur centimeter-scale assembly of structurally mature ~50 μm-diameter epithelial tubules that are locally self-organized, but globally programmed. Our approach prescribes tubule network geometry at ~5x smaller length-scales than currently possible using 3D printing, and at local cell densities comparable to in vivo tissues. Kinomorphs could be used to scaffold and “plumb” arrays of organoids in the future, by guiding the morphogenesis of epithelial networks. Such hybrid globally programmed/locally self-organized tissues address a major gap in our ability to recapitulate organ-scale tissue structure.Significance StatementEngineers are attempting to build tissues that mimic human diseases outside of the body. Although stem cells can be coaxed to form small organoids with a diversity of cell types, they do not properly organize over large distances by themselves. We report a strategy to mimic developmental processes using dynamic materials that attempt to guide a cellular “blueprint” towards a more complex tissue endpoint. We call these materials kinomorphs, combining the Greek kinó (propel, drive) and morfí (form, shape), since they seek to shepherd both the shape and developmental trajectory of cell collectives within them. Kinomorphs could pave the way towards organ-scale synthetic tissues built through a hybrid of engineering and self-organization strategies.
Cognitive and non-cognitive outcomes associated with student engagement in a novel brain chemoarchitecture mapping course-based undergraduate research experience
Authors: D’Arcy Christina E. , Martinez Anais , Khan Arshad M. , Olimpo Jeffrey T. 
Published: September 2019

AbstractCourse-based undergraduate research experiences (CUREs) engage emerging scholars in the authentic process of scientific discovery, and foster their development of content knowledge, motivation, and persistence in the science, technology, engineering, and mathematics (STEM) disciplines. Importantly, authentic research courses simultaneously offer investigators unique access to an extended population of students who receive education and mentoring in conducting scientifically relevant investigations and who are thus able to contribute effort toward big-data projects. While this paradigm benefits fields in neuroscience, such as atlas-based brain mapping of nerve cells at the tissue level, there are few documented cases of such laboratory courses offered in the domain.Here, we describe a curriculum designed to address this deficit, evaluate the scientific merit of novel student-produced brainatlasmapsofimmunohistochemically-identifiednervecellpopulations for the rat brain, and assess shifts in science identity, attitudes, and science communication skills of students engaged in the introductory-level Brain Mapping and Connectomics (BM&C) CURE. BM&C students reported gains in research and science process skills following participation in the course. Furthermore, BM&C students experienced a greater sense of science identity, including a greater likelihood to discuss course activities with non-class members compared to their non-CURE counterparts. Importantly, evaluation of student-generated brain atlas maps indicated that the course enabled students to produce scientifically valid products and make new discoveries to advance the field of neuroanatomy. Together, these findings support the efficacy of the BM&C course in addressing the relatively esoteric demands of chemoarchitectural brain mapping.
Ectopic methylation of a single persistently-unmethylated CpG in the promoter of the vitellogenin gene abolishes its inducibility by estrogen through attenuation of USF binding
Authors: Kallenberger Lia , Erb Rachel , Kralickova Lucie , Patrignani Andrea , Stöckli Esther , Jiricny Josef 
Published: September 2019

ABSTRACTThe enhancer/promoter of the vitellogenin II (VTG) gene has been extensively studied as a model system of vertebrate transcriptional control. While deletion mutagenesis andin vivofootprinting identified the transcription factor (TF) binding sites governing its tissue specificity, DNase hypersensitivity- and DNA methylation studies revealed the epigenetic changes accompanying its hormone-dependent activation. Moreover, upon induction with estrogen (E2), the region flanking the estrogen-responsive element (ERE) was reported to undergo active DNA demethylation. We now show that although theVTGERE is methylated in embryonic chicken liver and in LMH/2A hepatocytes, its induction by E2was not accompanied by extensive demethylation. In contrast, E2failed to activate aVTGenhancer/promoter-controlled luciferase reporter gene methylated bySssI. Surprisingly, this inducibility difference could be traced not to the ERE, but rather to a single CpG in an E-box (CACGTG) sequence upstream of theVTGTATA box, which is unmethylatedin vivo, but methylated bySssI. We demonstrate that this E-box binds the upstream stimulating factor USF1/2. Selective methylation of the CpG within this binding site with an E-box-specific DNA methyltranferaseEco72IM was sufficient to attenuate USF1/2 bindingin vitroand abolish the hormone-induced transcription of theVTGgene in the reporter system.
Discontinuous transcription of ribosomal DNA in human cells
Authors: Smirnov Evgeny , Trošan Peter , de Sousa Cabral João Victor , Studený Pavel , Kereïche Sami , Jirsová Kateřina , Cmarko Dušan 
Published: September 2019

AbstractNumerous studies show that various genes in all kinds of organisms are transcribed discontinuously, i.e. in short bursts or pulses with periods of inactivity between them. But it remains unclear whether ribosomal DNA (rDNA), represented by multiple copies in every cell, is also expressed in such manner. In this work, we synchronized the pol I activity in the populations of tumour derived as well as normal human cells by cold block and release. Then using special software for analysis of the microscopic images, we measured the intensity of transcription signal revealed by incorporated 5-fluorouridine (FU) in the nucleoli at different time points after the release. We found that the ribosomal genes in the human cells are transcribed discontinuously with periods ranging from 45 min to 75 min. Our data indicate that the dynamics of rDNA transcription follows the undulating pattern, in which the bursts are alternated by periods of rare transcription events.
A Bayesian approach to accurate and robust signature detection on LINCS L1000 data
Authors: Qiu Yue , Lu Tianhuan , Lim Hansaim , Xie Lei 
Published: September 2019

AbstractLINCS L1000 dataset produced by L1000 assay contains numerous cellular expression data induced by large sets of perturbagens. Although it provides invaluable resources for drug discovery as well as understanding of disease mechanisms, severe noise in the dataset makes the detection of reliable gene expression signals difficult. Existing methods for the peak deconvolution, eitherk-means based or Gaussian mixture model, cannot reliably recover the accurate expression level of genes in many cases, thereby limiting their robust applications in biomedical studies. Here, we have developed a novel Bayes’ theory based deconvolution algorithm that gives unbiased likelihood estimations for peak positions and characterizes the peak with a probability basedz-scores. Based on above algorithm, a pipeline is built to process raw data from L1000 assay into signatures that represent the features of perturbagen. The performance of the proposed new pipeline is rigorously evaluated using the similarity between bio-replicates and between drugs with shared targets. The results show that the new signature derived from the proposed algorithm gives a substantially more reliable and informative representation for perturbagens than existing methods. Thus, our new Bayesian-based peak deconvolution andz-score calculation method may significantly boost the performance of invaluable L1000 data in the down-stream applications such as drug repurposing, disease modeling, and gene function prediction.
Mechanotransduction of strain regulates an invasive phenotype in newly transformed epithelial cells
Authors: Chagnon-Lessard Sophie , Jean-Ruel Hubert , Godin Michel , Pelling Andrew E. 
Published: September 2019

AbstractOur organs and tissues are in constant motion, exposing epithelial cells to mechanical stretch. However, how these external forces impact cellular morphology, organization and dynamics in healthy and diseased tissues is still being elucidated. In several studies, we and others have shown how mechanical stresses and strains in the epithelium can modulate the dynamics and invasiveness of transformed cells. Carcinoma, the most common type of cancer, develops in the sheets of cells forming the epithelium and lining our organs and cavities. It usually begins with the transformation of a single cell via the activation of oncogenes such as Ras. Here, we show in a model system how mechanical stretch in epithelial sheets results in a more invasive phenotype in transformed cells.Cyclic strain prevents the formation of strong circumferential belts of actin in RasV12 cells and greatly promoting the formation of RasV12 protrusions, typical of a more invasive phenotype. We also show that RasV12 and wild type MDCK cells possess distinct sensitivity to strain. External forces remodel their actin cytoskeletons and adhesion complexes differently, resulting in a more invasive system dynamic. Our work demonstrates that the Rho-ROCK mechanotransduction pathway is involved in regulating a mechanically-induced switch to a more invasive phenotype. In a mechanically dynamic microenvironment, transformed cells exhibit drastically different cellular dynamics and movements when compared to static conditions. They grow larger invasive protrusions, potentially making them harder to be eliminated from healthy tissues. The insights gained in this study reveal the complex dynamics at play in healthy and transformed epithelial cells which are found in a mechanically active microenvironment.
Large-scale differential gene expression analysis identifies genes associated with Bipolar Disorder in post-mortem brain
Authors: Omar Mohamed N. , Youssef Mohamed , Abdellatif Mohamed 
Published: September 2019

ABSTRACTBackground and purposeBipolar disorder (BD) is a common psychiatric disorder with high morbidity and mortality. Several polymorphisms have been found to be implicated in the pathogenesis of BD, however, these loci have small effect sizes that fail to explain the high heritability of the disease. Here, we provide more insights into the genetic basis of BD by identifying the differentially expressed genes (DEGs) and their associated pathways and biological processes in post-mortem brain tissues of patients with BD.MethodsEight datasets were eligible for the differential expression analysis. We used six datasets for the discovery of the gene signature and used the other two for independent validation. We performed the multi-cohort analysis by a random-effect model using R and MetaIntegrator package.ResultsThe initial analysis resulted in the identification of 126 DEGs (30 up-regulated and 94 down-regulated). We refined this initial signature by a forward search process and resulted in the identification of 22 DEGs (6 up-regulated and 16 down-regulated). We validated the final gene signature in the independent datasets and resulted in an Area Under the ROC Curve (AUC) of 0.756 and 0.76, respectively. We performed gene set enrichment analysis (GSEA) which identified several biological processes and pathways related to BD including Ca transport, inflammation and DNA damage response.ConclusionOur findings support the previous findings that link BD pathogenesis to abnormalities in glial inflammation and calcium transport and also identify several other biological processes not previously reported to be associated with the development of the disease. Such findings will improve our understanding of the genetic basis underlying BD and may have future clinical implications.
GEO2RNAseq: An easy-to-use R pipeline for complete pre-processing of RNA-seq data
Authors: Seelbinder Bastian , Wolf Thomas , Priebe Steffen , McNamara Sylvie , Gerber Silvia , Guthke Reinhard , Linde Jörg 
Published: September 2019

ABSTRACTIn transcriptomics, the study of the total set of RNAs transcribed by the cell, RNA sequencing (RNA-seq) has become the standard tool for analysing gene expression. The primary goal is the detection of genes whose expression changes significantly between two or more conditions, either for a single species or for two or more interacting species at the same time (dual RNA-seq, triple RNA-seq and so forth). The analysis of RNA-seq can be simplified as many steps of the data pre-processing can be standardised in a pipeline.In this publication we present the “GEO2RNAseq” pipeline for complete, quick and concurrent pre-processing of single, dual, and triple RNA-seq data. It covers all pre-processing steps starting from raw sequencing data to the analysis of differentially expressed genes, including various tables and figures to report intermediate and final results. Raw data may be provided in FASTQ format or can be downloaded automatically from the Gene Expression Omnibus repository. GEO2RNAseq strongly incorporates experimental as well as computational metadata. GEO2RNAseq is implemented in R, lightweight, easy to install via Conda and easy to use, but still very flexible through using modular programming and offering many extensions and alternative workflows.GEO2RNAseq is publicly available at https://anaconda.org/xentrics/r-geo2rnaseq and https://bitbucket.org/thomas_wolf/geo2rnaseq/overview, including source code, installation instruction, and comprehensive package documentation.