bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laser interstitial thermal therapy in drug-resistant epilepsy
Authors: Shimamoto Shoichi , Wu Chengyuan , Sperling Michael R. 
Published: January 2019

Purpose of review
MRI-guided stereotactic laser interstitial thermal therapy (LiTT) has been utilized in the surgical treatment of discrete, small epileptogenic lesions. This review summarizes the current literature and addresses the clinical application of this technique.

Recent findings
LiTT has the potential to reduce the morbidity and discomfort of epilepsy surgery. Review of data from retrospective, uncontrolled studies suggests that LiTT may offer benefit when treating drug-resistant epilepsy because of mesial temporal sclerosis, hypothalamic hamartoma, cavernous hemangioma, and small cortical dysplasias and malformations. It is now being offered as initial therapy in place of anterior temporal lobectomy in many centers, and a prospective study is underway to compare it with historical temporal lobectomy reports.

Summary
LiTT appears promising and has potential for reduced morbidity and improved tolerability compared with open surgery. Studies must be done to compare efficacy and safety of LiTT with open surgery, and further investigation is needed to optimize this technique.
Nonparaneoplastic autoimmune cerebellar ataxias
Authors: Joubert Bastien , Honnorat Jerome 
Published: January 2019

Purpose of review
The current review develops the clinical presentations of nonparaneoplastic autoimmune cerebellar ataxia (ACA) and analyzes the association with autoantibodies.

Recent findings
Emerging evidence suggests that autoimmunity is involved in a significant proportion of sporadic ataxia cases. Moreover, numerous autoantibodies have recently been described in association with sporadic cerebellar ataxia, improving diagnosis and patient categorization.

Summary
Nonparaneoplastic ACA encompasses postinfectious acute cerebellar ataxia, opsoclonus-myoclonus-ataxia syndrome, and pure cerebellar ataxia with or without autoantibodies. There is still confusion about how to diagnose and classify the patients, and retrospective data suggest that these very rare entities are in fact largely underrecognized. Numerous autoantibodies have been found associated with sporadic ataxia, improving diagnosis accuracy, and patient categorization. However, although anti-glutamate decarboxylase isotype 65 (GAD65), anti-contactin-associated protein 2 (CASPR2), and anti metabotropic glutamate receptor (mGluR1) antibodies are well recognized biomarkers, many other autoantibodies have been described in very small numbers of patients and their specificity is unknown. Efficient biomarkers for ACA are still lacking and in many cases the diagnosis has to rely on a body of converging evidence.
Supranormal Sensory Nerve Action Potential Amplitude Correlates of Sensory Symptoms
Authors: Tipton Philip W. , Rubin Devon I. 
Published: January 2019

Purpose:
Patients presenting with pain, numbness, or paresthesias frequently have normal electrodiagnostic studies. Supranormal sensory nerve action potential amplitudes may be a potential biomarker of sensory nerve hyperexcitability.

Methods:
A retrospective chart review of 400 consecutive patients with normal electromyography reports between July and November 2016 was performed. Patients were divided into tertiles based on the degree of sensory nerve action potential amplitudes above lower limits of normal (<2×, 2–3×, and >3×). Patient demographics and sensory symptom quality were assessed. Multivariate analysis assessed for an association between sensory symptoms and sensory nerve action potential amplitudes, age, or gender.

Results:
After controlling for age and gender, subjects in the 2–3× and >3× normal tertiles had a higher association with multifocal symptoms, whereas those in the >3× normal tertile had a lower association with distal symptoms compared with the <2× normal tertile.

Conclusion:
The association of supranormal sensory nerve action potential amplitudes with multifocal symptoms may be an indicator of diffuse hyperexcitability.
Attitudes Toward Electroconvulsive Therapy Among Involuntary and Voluntary Patients
Authors: Takamiya Akihiro , Sawada Kyosuke , Mimura Masaru , Kishimoto Taishiro 
Published: January 2019

Objective
We aimed to examine attitudes toward electroconvulsive therapy (ECT) among involuntary patients, voluntary patients, and their relatives.

Methods
Patients experiencing a major depressive episode and receiving ECT and their relatives were recruited for the survey. Patients and their relatives answered the self-rating questionnaires with a 7-point Likert scale. We explored differences in the survey results between involuntary and voluntary patients, as well as differences in the survey results between patients and their relatives.

Results
We recruited 97 participants (53 patients and 44 relatives) for the survey. Approximately 80% of the patients showed positive attitudes toward ECT. There were no statistically significant differences between involuntary (n = 23) and voluntary (n = 30) patients across multiple aspects of the ECT experience, including treatment satisfaction, positive or adverse effects of ECT, and treatment preference in the future. Relatives were more satisfied with the positive effects of ECT and with the information offered before ECT treatment than the patients themselves.

Conclusions
Approximately 80% of the patients showed overall satisfaction with ECT irrespective of consent status. Relatives were more satisfied with ECT than patients. Electroconvulsive therapy can be a lifesaving treatment for severely depressed patients, and the subjective experience of involuntary patients should be taken into consideration when discussing involuntary ECT treatment.
lncRNA Neat1 drives neuronal histone methylation and age-related memory impairments
Authors: Butler Anderson A. , Johnston Daniel R. , Kaur Simranjit , Lubin Farah D. 
Published: January 2019

AbstractHistone methylation is critical for the formation and maintenance of long-term memories. Long noncoding RNAs (lncRNAs) are regulators of histone methyltransferases and other chromatin modifying enzymes (CMEs). We investigated how lncRNA Neat1-mediated histone methylation contributes to hippocampus-dependent long-term memory formation, using a combination of transcriptomics, RNA binding protein immunoprecipitation, CRISPR mediated gene activation, and behavioral approaches. Suppression of the lncRNA Neat1 revealed widespread changes in gene transcription as well as perturbations of histone 3 lysine 9 dimethylation (H3K9me2), a repressive histone modification mark that is dysregulated in the aging hippocampus. We identified a Neat1-dependent mechanism of transcriptional repression via H3K9me2 at the c-Fos promoter corresponding with observed changes in c-Fos mRNA levels. Overexpression of hippocampal Neat1 via CRISPRa is sufficient to impair memory formation in young adults, recapitulating observed memory deficits in old adults, while Neat1 suppression in both young and old adult mice improves memory. These results suggest that lncRNA Neat1 is a potent epigenetic regulator of hippocampus-dependent long-term memory formation.
G4-iM Grinder: DNA and RNA G-Quadruplex, i-Motif and higher order structure search and analyser tool
Authors: Belmonte-Reche Efres , Morales Juan Carlos 
Published: January 2019

ABSTRACTHerein, we present G4-iM Grinder as a system for potential G4, i-Motif and higher-order structure identification and characterization. Several grading tools of biological relevance and G4 in vitro formation probability are included in this highly modulable and robust engine. G4-iM Grinder improves other current quadruplex search engines when compared in capabilities and processing time. We used G4-iM Grinder in the analysis of the complete human genome whilst focusing on frequency and score of G-based structures. We studied the most recurrent potential quadruplex sequences (PQS) and the longest highest scoring potential higher order quadruplex sequences (PHOQS) in our genome. As proof of the analytical capabilities of G4-iM Grinder, we also analysed a new PHOQS and predicted the most probable PQS subunits to form it. Taking the human average PQS density as reference, we examined the genomes of organisms that cause leishmaniosis, diphtheria, brucellosis, meningitis, pneumonia, toxoplasmosis, tuberculosis, leprosy, AIDS, dengue fever and hepatitis C, and found they are very rich in PQS. G4-iM Grinder identified within many of these organisms several already known-to-form G4 sequences. Together, this suggests that G4-quadruplexes may potentially be important therapeutic targets against many of these organisms that currently kill millions worldwide.GRAPHICAL ABSTRACT
Completing the ENCODE3 compendium yields accurate imputations across a variety of assays and human biosamples
Authors: Schreiber Jacob , Bilmes Jeffrey , Stafford Noble William 
Published: January 2019

AbstractMotivationRecent efforts to describe the human epigenome have yielded thousands of uniformly processed epigenomic and transcriptomic data sets. These data sets characterize a rich variety of biological activity in hundreds of human cell lines and tissues (“biosamples”). Understanding these data sets, and specifically how they differ across biosamples, can help explain many cellular mechanisms, particularly those driving development and disease. However, due primarily to cost, the total number of assays that can be performed is limited. Previously described imputation approaches, such as Avocado, have sought to overcome this limitation by predicting genome-wide epigenomics experiments using learned associations among available epigenomic data sets. However, these previous imputations have focused primarily on measurements of histone modification and chromatin accessibility, despite other biological activity being crucially important.ResultsWe applied Avocado to a data set of 3,814 tracks of data derived from the ENCODE compendium, spanning 400 human biosamples and 84 assays. The resulting imputations cover measurements of chromatin accessibility, histone modification, transcription, and protein binding. We demonstrate the quality of these imputations by comprehensively evaluating the model’s predictions and by showing significant improvements in protein binding performance compared to the top models in an ENCODE-DREAM challenge. Additionally, we show that the Avocado model allows for efficient addition of new assays and biosamples to a pre-trained model, achieving high accuracy at predicting protein binding, even with only a single track of training data.AvailabilityTutorials and source code are available under an Apache 2.0 license at https://github.com/jmschrei/avocado.Contactwilliam-noble@uw.edu or jmschr@cs.washington.edu
A novel plasmid-transcribed regulatory sRNA, QfsR, controls chromosomal polycistronic mRNAs in Agrobacterium tumefaciens
Authors: Diel Benjamin , Dequivre Magali , Wisniewski-Dyé Florence , Vial Ludovic , Hommais Florence 
Published: January 2019

AbstractPlasmids are mobile DNAs that adjust host cell functions for their own amplification and dissemination. We identified QfsR, a small RNA, transcribed from the Ti plasmid in the phytopathogen Agrobacterium fabrum. QfsR is widely conserved throughout RepABC plasmids carried by Rhizobiaceae. Target prediction, expression analysis and site-direct mutagenesis experiments show that QfsR directly pairs within polycistronic mRNAs transcribed from chromosomes (involved in flagella apparatus and succinoglycan biosynthesis) and Ti plasmid (involved in conjugative transfer). QfsR leads to a coordinated expression of whole polycistronic mRNA molecules. Whereas a lack of QfsR induces motility and reduces succinoglycan production, its overproduction increases the quorum sensing signal accumulation and the Ti plasmid conjugative transfer. Based on these observations, we propose QfsR as a hub connecting regulatory networks of motility, succinoglycan biosynthesis and plasmid conjugative transfer. To our knowledge, QfsR is the first example of a plasmid-encoded sRNA that controls chromosomal polycistronic mRNAs.SignificancePlasmids represent an important cost for the hosting cell although some are beneficial under certain circumstances. Agrobacterium tumefaciens harboring Tumor inducing plasmid (pTi) are able to infect plants and to use specific resources produced by the infected cells. We characterized QfsR, a novel small RNA (sRNA) from pTi, that directly regulates plasmid polycistronic mRNA but also chromosomal ones. QfsR contributes to a fine-tuned regulation of bacterial motility, exopolysaccharide biosynthesis and conjugative dissemination of pTi. Our results report the first plasmid-encoded sRNA able to modify and coordinate cellular behaviour probably for the benefit of the plasmid dissemination and tight crosstalk between plasmid and chromosome. This could be widespread since QfsR homologs were predicted in other plasmids of Rhizobiaceae symbionts and pathogens.
The International Space Station selects for microorganisms adapted to the extreme environment, but does not induce genomic and physiological changes relevant for human health
Authors: Mora Maximilian , Wink Lisa , Kögler Ines , Mahnert Alexander , Rettberg Petra , Schwendner Petra , Demets René , Cockell Charles , Alekhova Tatiana , Klingl Andreas , Alexandrova Alina , Moissl-Eichinger Christine 
Published: January 2019

AbstractThe International Space Station (ISS) is a unique, completely confined habitat for the human crew and co-inhabiting microorganisms. Here, we report on the results of the ISS experiment “EXTREMOPHILES”. We aimed to exploit the microbial information obtained from three surface and air sampling events aboard the International Space Station during increments 51 and 52 (2017) with respect to: i) microbial sources, diversity and distribution within the ISS, ii) functional capacity of microbiome and microbial isolates, iii) extremotolerance and antibiotics-resistance (compared to ground controls), and iv) microbial behavior towards ISS-relevant materials such as biofilm formation, or potential for degradation. We used wipe samples and analyzed them by amplicon and metagenomics sequencing, cultivation, comparative physiological studies, antibiotic resistance tests, genome analysis of isolates and co-incubation experiments with ISS-relevant materials. The major findings were: i) the ISS microbiome profile is highly similar to ground-based confined indoor environments, ii) the ISS microbiome is subject to fluctuations and indicative for the (functional) location, although a core microbiome was present over time and independent from location, iii) the ISS selects for microorganisms adapted to the extreme environment, but does not necessarily induce genomic and physiological changes which might be relevant for human health, iv) cleanrooms and cargo seems to be a minor source of microbial contamination aboard, and v) microorganisms can attach to and grow on ISS-relevant materials. Biofilm formation might be a threat for spacecraft materials with the potential to induce instrument malfunctioning with consequences for mission success. We conclude that our data do not raise direct reason for concern with respect to crew health, but indicate a potential threat towards biofilm formation and material integrity in moist areas.
Centromere-mediated chromosome break drives karyotype evolution in closely relatedMalasseziaspecies
Authors: Sankaranarayanan Sundar Ram , Ianiri Giuseppe , Reza Md. Hashim , Thimmappa Bhagya C. , Ganguly Promit , Coelho Marco A. , Sun Sheng , Siddharthan Rahul , Tellgren-Roth Christian , Dawson Thomas L , Heitman Joseph , Sanyal Kaustuv 
Published: January 2019

AbstractIntra-chromosomal or inter-chromosomal genomic rearrangements often lead to speciation (1). Loss or gain of a centromere leads to alterations in chromosome number in closely related species. Thus, centromeres can enable tracing the path of evolution from the ancestral to a derived state (2). TheMalasseziaspecies complex of the phylum Basiodiomycota shows remarkable diversity in chromosome number ranging between six and nine chromosomes (3–5). To understand these transitions, we experimentally identified all eight centromeres as binding sites of an evolutionarily conserved outer kinetochore protein Mis12/Mtw1 inM. sympodialis. The 3 to 5 kb centromere regions share an AT-rich, poorly transcribed core region enriched with a 12 bp consensus motif. We also mapped nine such AT-rich centromeres inM. globosaand the related speciesMalassezia restrictaandMalassezia slooffiae. While eight predicted centromeres were found within conserved synteny blocks between these species andM. sympodialis, the remaining centromere inM. globosa(MgCEN2) or its orthologous centromere inM. slooffiae(MslCEN4) andM. restricta(MreCEN8) mapped to a synteny breakpoint compared withM. sympodialis. Taken together, we provide evidence that breakage and loss of a centromere (CEN2) in an ancestralMalasseziaspecies possessing nine chromosomes resulted in fewer chromosomes inM. sympodialis. Strikingly, the predicted centromeres of all closely relatedMalasseziaspecies map to an AT-rich core on each chromosome that also shows enrichment of the 12 bp sequence motif. We propose that centromeres are fragile AT-rich sites driving karyotype diversity through breakage and inactivation in these and other species.Significance statementThe number of chromosomes can vary between closely related species. Centromere loss destabilizes chromosomes and results in reduced number of chromosomes to drive speciation. A series of evidence from studies on various cancers suggest that an imbalance in kinetochore-microtubule attachments results in breaks at the centromeres. To understand if such events can cause chromosome number changes in nature, we studied six species ofMalassezia, of which three possess eight chromosomes and others have nine chromosomes each. We find signatures of chromosome breakage at the centromeres in organisms having nine chromosomes. We propose that the break at the centromere followed by fusions of acentric chromosomes to other chromosomes could be a plausible mechanism shaping the karyotype ofMalasseziaand related organisms.ClassificationBiological sciences, Genetics
Genome-wide assessment ofMycobacterium tuberculosisconditionally essential metabolic pathways
Authors: Minato Yusuke , Gohl Daryl M , Thiede Joshua M. , Chacón Jeremy M. , Harcombe William R. , Maruyama Fumito , Baughn Anthony D. 
Published: January 2019

AbstractBetter understanding of essential cellular functions in pathogenic bacteria is important for the development of more effective antimicrobial agents. We performed a comprehensive identification of essential genes inMycobacterium tuberculosis, the major causative agent of tuberculosis, using a combination of transposon insertion sequencing (Tn-seq) and comparative genomic analysis. To identify conditional essential genes by Tn-seq, we used media with different nutrient composition. Although many conditional gene essentialities were affected by the presence of relevant nutrient sources, we also found that the essentiality of genes in a subset of metabolic pathways was unaffected by metabolites. Comparative genomic analysis revealed that not all essential genes identified by Tn-seq were fully conserved within theM. tuberculosiscomplex including some existing anti-tubercular drug target genes. In addition, we utilized an availableM. tuberculosisgenome-scale metabolic model, iSM810, to predictM. tuberculosisgene essentialityin silico. Comparing the sets of essential genes experimentally identified by Tn-seq to those predictedin silicoreveals the capabilities and limitations of gene essentiality predictions highlighting the complexity ofM. tuberculosisessential metabolic functions. This study provides a promising platform to study essential cellular functions inM. tuberculosis.Author SummaryMycobacterium tuberculosiscauses 10 million cases of tuberculosis (TB) each year resulting in over one million deaths. TB therapy is challenging because it requires a minimum of six months of treatment with multiple drugs. Protracted treatment times and the emergent spread of drug resistant TB necessitate the identification of novel targets for drug discovery to curb this global health threat. Essential functions, defined as those indispensable for growth and/or survival, are potential targets for new antimicrobial drugs. In this study, we aimed to define gene essentialities ofM. tuberculosison a genome-wide scale to comprehensively identify potential targets for drug discovery. We utilized a combination of experimental (functional genomics) andin silicoapproaches (comparative genomics and flux balance analysis). Our functional genomics approach identified sets of genes whose essentiality was affected by nutrient availability. Comparative genomics revealed that not all essential genes were fully conserved within theM. tuberculosiscomplex. Comparing sets of essential genes identified by functional genomics to those predicted by flux balance analysis highlighted gaps in current knowledge regardingM. tuberculosismetabolic capabilities. Thus, our study identifies numerous potential anti-tubercular drug targets and provides a comprehensive picture of the complexity ofM. tuberculosisessential cellular functions.
Identifying and ranking potential driver genes of Alzheimer’s Disease using multi-view evidence aggregation
Authors: Mukherjee Sumit , Perumal Thanneer , Daily Kenneth , Sieberts Solveig , Omberg Larsson , Preuss Christoph , Carter Gregory , Mangravite Lara , Logsdon Benjamin 
Published: January 2019

ABSTRACTMotivationLate onset Alzheimers disease (LOAD) is currently a disease with no known effective treatment options. To address this, there have been a recent surge in the generation of multi-modality data (Hodes and Buckholtz, 2016; Muelleret al., 2005) to understand the biology of the disease and potential drivers that causally regulate it. However, most analytic studies using these data-sets focus on uni-modal analysis of the data. Here we propose a data-driven approach to integrate multiple data types and analytic outcomes to aggregate evidences to support the hypothesis that a gene is a genetic driver of the disease. The main algorithmic contributions of our paper are: i) A general machine learning framework to learn the key characteristics of a few known driver genes from multiple feature-sets and identifying other potential driver genes which have similar feature representations, and ii) A flexible ranking scheme with the ability to integrate external validation in the form of Genome Wide Association Study (GWAS) summary statistics. While we currently focus on demonstrating the effectiveness of the approach using different analytic outcomes from RNA-Seq studies, this method is easily generalizable to other data modalities and analysis types.ResultsWe demonstrate the utility of our machine learning algorithm on two benchmark multi-view datasets by significantly outperforming the baseline approaches in predicting missing labels. We then use the algorithm to predict and rank potential drivers of Alzheimers. We show that our ranked genes show a significant enrichment for SNPs associated with Alzheimers, and are enriched in pathways that have been previously associated with the disease.AvailabilitySource code and link to all feature sets is availabile athttps://github.com/Sage-Bionetworks/EvidenceAggregatedDriverRanking.Contactben.logsdon@sagebionetworks.org