bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychotropic Medication Effects on Seizure Threshold and Seizure Duration During Electroconvulsive Therapy Stimulus Titration
Authors: Chiao Stephanie , Isenberg Keith , North Carol S. 
Published: October 2019

Objectives
Decisions about psychotropic medication administration before electroconvulsive therapy (ECT) are central to management of a very psychiatrically ill patient population. Given that many psychotropic medications are thought to either promote or prevent seizures, there is ongoing concern about concurrent psychotropic medication and ECT administration. This study examined the effect of psychotropic medications on seizure threshold and duration during ECT stimulus titration.

Methods
The study sample consisted of 550 patients receiving ECT stimulus titration at a single site during a 27-month period. Systematic chart review provided clinical data, including patients' demographics, psychiatric diagnoses, medications administered in the 48 hours before ECT, and information on the ECT procedure. Referring psychiatrists were advised to discontinue lithium before ECT but otherwise managed psychotropic medications as clinically indicated. A fixed charge titration schedule was used to estimate seizure threshold. Electroconvulsive therapy motor seizure duration was estimated by the cuff method, and electroencephalogram seizure duration was estimated by review of a 2-lead strip.

Results
Administration of psychotropic medications, including benzodiazepines, antiepileptics, selective serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, bupropion, and stimulants, was not associated with seizure threshold as estimated by electrical charge eliciting a generalized seizure or duration during the initial ECT titration. Tricyclic and tetracyclic antidepressant dosage was associated with seizure threshold.

Conclusions
Psychotropic medications may have little effect on seizure threshold and duration during titration of electrical dose at ECT initiation. Integrating this work with other literature supports making recommendations for medication discontinuation before ECT on an individual basis.
Cardiac structure and function in schizophrenia: a cardiac MR imaging study
Authors: Osimo Emanuele F. , Brugger Stefan P. , de Marvao Antonio , Pillinger Toby , Whitehurst Thomas , Statton Ben , Quinlan Marina , Berry Alaine , Cook Stuart A. , O’Regan Declan P. , Howes Oliver D. 
Published: October 2019

AbstractBackgroundHeart disease is the leading cause of death in schizophrenia.AimsWe investigated cardiac structure and function in patients with schizophrenia using cardiac magnetic resonance imaging (CMR) after excluding medical and metabolic comorbidity.Methods80 participants underwent CMR to determine biventricular volumes and function and measures of blood pressure, physical activity, and glycated haemoglobin levels. Patients and controls were matched for age, sex, ethnicity, and body surface area.ResultsPatients with schizophrenia had significantly smaller indexed left ventricular (LV) end-diastolic volume, end-systolic volume, stroke volume, right ventricular (RV) end-diastolic volume, end-systolic volume, and stroke volume but unaltered ejection fractions relative to controls. LV concentricity and septal thickness were significantly larger in schizophrenia. The findings were largely unchanged after adjusting for smoking or exercise levels and were independent of medication dose and duration.ConclusionsPatients with schizophrenia show evidence of prognostically-adverse cardiac remodelling compared to matched controls, independent of conventional risk factors.
FUS-dependent liquid-liquid phase separation is an early event in double-strand break repair
Authors: Levone Brunno R. , Lenzken Silvia C. , Antonaci Marco , Maiser Andreas , Rapp Alexander , Conte Francesca , Reber Stefan , Ronchi Antonella E. , Mühlemann Oliver , Leonhardt Heinrich , Cardoso M. Cristina , Ruepp Marc-David , Barabino Silvia M.L. 
Published: October 2019

AbstractRNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair, and it undergoes reversible liquid-liquid phase separation (LLPS)in vitro. Here, we demonstrate that FUS-dependent LLPS is necessary for the initiation of the DDR. Using laser microirradiation in FUS-knockout cells, we show that FUS is required for the recruitment to DNA damage sites of the DDR factors KU80, NBS1, 53BP1, and of SFPQ, another RBP implicated in the DDR. The relocation of KU80, NBS1, and SFPQ is similarly impaired by LLPS inhibitors, or LLPS-deficient FUS variants. We also show that LLPS is necessary for efficient γH2AX foci formation. Finally, using super-resolution structured illumination microscopy, we demonstrate that the absence of FUS impairs the proper arrangement of γH2AX nano-foci into higher-order clusters. These findings demonstrate the early requirement for FUS-dependent LLPS in the activation of the DDR and the proper assembly of DSBs repair complexes.
DAMEfinder: A method to detect differential allele-specific methylation
Authors: Orjuela Stephany , Machlab Dania , Menigatti Mirco , Marra Giancarlo , Robinson Mark D. 
Published: October 2019

AbstractDNA methylation is a highly studied epigenetic signature that is associated with regulation of gene expression, whereby genes with high levels of promoter methylation are generally repressed. Genomic imprinting occurs when one of the parental alleles is methylated, i.e, when there is inherited allele-specific methylation (ASM). A special case of imprinting occurs during X chromosome inactivation in females, where one of the two X chromosomes is silenced, in order to achieve dosage compensation between the sexes. Another more widespread form of ASM is sequence dependent (SD-ASM), where ASM is linked to a nearby heterozygous single nucleotide polymorphism (SNP).We developed a method to screen for genomic regions that exhibit loss or gain of ASM in samples from two conditions (treatments, diseases, etc.). The method relies on the availability of bisulfite sequencing data from multiple samples of the two conditions. We leverage other established computational methods to screen for these regions within a new R package called DAMEfinder. It calculates an ASM score for all CpG sites or pairs in the genome of each sample, and then quantifies the change in ASM between conditions. It then clusters nearby CpG sites with consistent change into regions.In the absence of SNP information, our method relies only on reads to quantify ASM. This novel ASM score compares favourably to current methods that also screen for ASM. Not only does it easily discern between imprinted and non-imprinted regions, but also females from males based on X chromosome inactivation. We also applied DAMEfinder to a colorectal cancer dataset and observed that colorectal cancer subtypes are distinguishable according to their ASM signature. We also re-discover known cases of loss of imprinting.We have designed DAMEfinder to detect regions of differential ASM (DAMEs), which is a more refined definition of differential methylation, and can therefore help in breaking down the complexity of DNA methylation and its influence in development and disease.
Genomic profiling of plasma circulating tumor DNA reveals genetics and residual disease in extranodal NK/T-cell lymphoma
Authors: Li Qiong , Zhang Wei , Li Jiali , Xiong Jingkang , Liu Jia , Chen Ting , Wen Qin , Zeng Yunjing , Gao Li , Gao Lei , Zhang Cheng , Kong Peiyan , Liu Yao , Zhang Xi , Rao Jun 
Published: October 2019

AbstractBackgroundExtranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive hematological malignancy with poor prognosis. Early detection of tumors at initial diagnosis or during routine surveillance is important for improving survival outcomes. Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool for monitoring disease status. Here, we investigated the feasible of ctDNA detection in ENTKL.MethodsPlasma ctDNA was assessment were based on blood specimens that were collected from 65 patients recently diagnosed with ENKTL at the hematology medical center of Xinqiao Hospital, longitudinal samples collected under chemotherapy also included. Gene mutation spectrum of ENKTL was analyzed via cancer personalized profiling sequencing (CAPP-Seq). This study is registered with ClinicalTrials.gov (ChiCTR1800014813)ResultsFrom February 2017 to September 2019, 65 patients were enrolled, we found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%), NOTCH1 (7.7%). The mutation frequencies of KMT2D was significantly higher in stage III-IV, and mutations in KMT2D, ASXL3 and JAK3 were significantly correlated with the metabolic tumor burden of the patients. Compared with tumor tissue DNA, ctDNA profiling showed good concordance. Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequency of genes. Compared with PET/CT, ctDNA has more advantages for tracking residual disease in patients. In addition, we also found that mutated KMT2D predicted poor prognosis in patients.ConclusionCollectively, our results provide evidence that ctDNA may serve as a novel precision medicine biomarker in ENKTL.
Control of Social Withdrawal of Mice Deficient for the Autism Gene Magel2 by Restoration of Vasopressin-Oxytocin Dialogue in Septum
Authors: Borie Amélie M. , Dromard Yann , Dufner Djodi , Pollozi Emi , Huzard Damien , Tömböli Csaba , Olma Aleksandra , Manning Maurice , Colson Pascal , Guillon Gilles , Muscatelli Françoise , Desarménien Michel G. , Jeanneteau Freddy 
Published: October 2019

SummaryIntellectual and social disabilities are common comorbidities in adolescents and adults with Magel2 gene deficiency characterizing the Prader-Willi and Schaaf-Yang neurodevelopmental syndromes. The cellular and molecular mechanisms underlying the risk for autism in these syndromes are unexplored. Here we used Magel2 knockout mice combined with optogenetic/pharmacological tools to characterize disease modifications in the social brain network. We find that the degree of social novelty moderates a dialogue between vasopressin and oxytocin in the lateral septum, a region organizing sequential content of sensory experiences. Social withdrawal of mice lacking Magel2 is alleviated by restoration of dialogue-lead by vasopressin. This preclinical study identifies the collective actions of vasopressin and oxytocin in the lateral septum as a key factor in the pathophysiology.
Genomes of Symbiodiniaceae reveal extensive sequence divergence but conserved functions at family and genus levels
Authors: González-Pech Raúl A. , Chen Yibi , Stephens Timothy G. , Shah Sarah , Mohamed Amin R. , Lagorce Rémi , Bhattacharya Debashish , Ragan Mark A. , Chan Cheong Xin 
Published: October 2019

AbstractDinoflagellates of the family Symbiodiniaceae (Order Suessiales) are predominantly symbiotic, and many are known for their association with corals. The genetic and functional diversity among Symbiodiniaceae is well acknowledged, but the genome-wide sequence divergence among these lineages remains little known. Here, we present de novo genome assemblies of five isolates from the basal genus Symbiodinium, encompassing distinct ecological niches. Incorporating existing data from Symbiodiniaceae and other Suessiales (15 genome datasets in total), we investigated genome features that are common or unique to these Symbiodiniaceae, to genus Symbiodinium, and to the individual species S. microadriaticum and S. tridacnidorum. Our whole-genome comparisons reveal extensive sequence divergence, with no sequence regions common to all 15. Based on similarity of k-mers from whole-genome sequences, the distances among Symbiodinium isolates are similar to those between isolates of distinct genera. We observed extensive structural rearrangements among symbiodiniacean genomes; those from two distinct Symbiodinium species share the most (853) syntenic gene blocks. Functions enriched in genes core to Symbiodiniaceae are also enriched in those core to Symbiodinium. Gene functions related to symbiosis and stress response exhibit similar relative abundance in all analysed genomes. Our results suggest that structural rearrangements contribute to genome sequence divergence in Symbiodiniaceae even within a same species, but the gene functions have remained largely conserved in Suessiales. This is the first comprehensive comparison of Symbiodiniaceae based on whole-genome sequence data, including comparisons at the intra-genus and intra-species levels.
Conditional knockout of RAD51-related genes inLeishmania majorreveals a critical role for homologous recombination during genome replication
Authors: Damasceno Jeziel D. , Reis-Cunha João , Crouch Kathryn , Lapsley Craig , Tosi Luiz R. O. , Bartholomeu Daniella , McCulloch Richard 
Published: October 2019

AbstractHomologous recombination (HR) has an intimate relationship with genome replication, both during repair of DNA lesions that might prevent DNA synthesis and in tackling stalls to the replication fork. Recent studies led us to ask if HR might have a more central role in replicating the genome ofLeishmania, a eukaryotic parasite. Conflicting evidence has emerged regarding whether or not HR genes are essential, and genome-wide mapping has provided evidence for an unorthodox organisation of DNA replication initiation sites, termed origins. To answer this question, we have employed a combined CRISPR/Cas9 and DiCre approach to rapidly generate and assess the effect of conditional ablation of RAD51 and three RAD51-related proteins inLeishmania major. Using this approach, we demonstrate that loss of any of these HR factors is not immediately lethal, but in each case growth slows with time and leads to DNA damage, accumulation of cells with aberrant DNA content, and genome-wide mutation. Despite these similarities, we show that only loss of RAD51 and RAD51-3 impairs DNA synthesis, and that the factors act in distinct ways. Finally, we reveal that loss of RAD51 has a profound effect on DNA replication, causing loss of initiation at the major origins and increased DNA synthesis at subtelomeres. Our work clarifies questions regarding the importance of HR to survival ofLeishmaniaand reveals an unanticipated, central role for RAD51 in the programme of genome replication in a microbial eukaryote.
Properties of rhizosphere soil associated with herbaceous plant roots analyzed using small-scale protocols
Authors: Yamazaki Shinichi , Ochiai Kumiko , Motokawa Junko , Hamamoto Shoichiro , Sugiyama Akifumi , Kobayashi Masaru 
Published: October 2019

AbstractThe rhizosphere, which is the region of soil adjacent to plant roots, is affected by the activities of both plant roots and associated microorganisms which cause changes in soil properties including nutrient mineral composition. Accordingly, the actual availability of plant nutrients may not be the same as that estimated on the basis of bulk soil analysis. However, the extent and manner in which the availability of plant nutrients in bulk and rhizosphere soils differ remain unclear. Therefore, the present study defined the rhizosphere as the soil adhered to plant roots, established a set of small-scale protocols for analyzing the nutrient minerals of small soil samples, and then characterized the rhizosphere soil of sorghum, Sorghum bicolor (L.) Moench. The mineral contents of the bulk and rhizosphere soil differed significantly, with nutrient contents generally greater in the rhizosphere, and particularly remarkable accumulation was observed in regards to ammonium ion and exchangeable potassium concentrations. Such accumulation might be due, in part, to the greater per weight surface areas of rhizosphere soil particles, but other mechanisms, including the accumulation of organic matter, could also be involved.
Multi-timescale hybrid components of the functional brain connectome: A bimodal EEG-fMRI decomposition
Authors: Wirsich Jonathan , Amico Enrico , Giraud Anne-Lise , Goñi Joaquín , Sadaghiani Sepideh 
Published: October 2019

Concurrent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) bridge brain connectivity across timescales. During concurrent EEG-fMRI resting-state recordings, whole-brain functional connectivity (FC) strength is spatially correlated across modalities. However, cross-modal investigations have commonly remained correlational, and joint analysis of EEG-fMRI connectivity is largely unexplored.Here we investigated if there exist (spatially) independent FC networks linked between modalities. We applied the recently proposed hybrid connectivity independent component analysis (connICA) framework to two concurrent EEG-fMRI resting state datasets (total 40 subjects). Two robust components were found across both datasets. The first component has a uniformly distributed EEG-frequency fingerprint linked mainly to intrinsic connectivity networks (ICNs) in both modalities. Conversely, the second component is sensitive to different EEG-frequencies and is primarily linked to intra-ICN connectivity in fMRI but to inter-ICN connectivity in EEG.The first hybrid component suggests that connectivity dynamics within well-known ICNs span timescales, from millisecond-range in all canonical frequencies of FCEEGto second-range of FCfMRI. Conversely, the second component additionally exposes linked but spatially divergent neuronal processing at the two timescales. This work reveals the existence of joint spatially independent components, suggesting that parts of resting-state connectivity are co-expressed in a linked manner across EEG and fMRI over individuals.
Chromatiblock: scalable whole-genome visualization of structural differences in prokaryotes
Authors: Sullivan Mitchell John , van Bakel Harm 
Published: October 2019

AbstractSummaryChromatiblock is a Python application for visualizing the presence, absence and arrangement of syntenic blocks across large numbers of complete bacterial genomes.AvailabilityChromatiblock is freely available under a GPL license, for macOS, GNU/Linux and and Microsoft Windows from https://github.com/mjsull/chromatiblock/Contactharm.vanbakel@mssm.edu
Heterogeneity in VEGF Receptor-2 mobility and organization on the endothelial cell surface leads to diverse activation models by VEGF
Authors: da Rocha-Azevedo Bruno , Lee Sungsoo , Dasgupta Aparajita , Vega Anthony R. , de Oliveira Luciana R. , Kim Tae , Kittisopikul Mark , Jaqaman Khuloud 
Published: October 2019

SummaryThe nanoscale organization of cell surface receptors plays an important role in signaling. We determined this organization and its relation to receptor activation for VEGF Receptor-2 (VEGFR-2), a critical receptor tyrosine kinase in endothelial cells (ECs), by combining live-cell single-molecule imaging of endogenous VEGFR-2 with rigorous computational analysis. We found that surface VEGFR-2 can be mobile or immobile/confined, and monomeric or non-monomeric, with a complex interplay between the two. The mobility and interaction heterogeneity of VEGFR-2 in the basal state led to heterogeneity in the sequence of steps leading to VEGFR-2 activation by VEGF. Specifically, we found that VEGF can bind to both monomeric and non-monomeric VEGFR-2, and, when binding to monomeric VEGFR-2, promotes dimer formation but only for immobile/confined receptors. Overall, our study highlights the dynamic and heterogeneous nature of cell surface receptor organization and its complex relationships with receptor activation and signaling.
Tailor-made sRNAs: a toolbox to control metabolic targets
Authors: Apura Patrícia , Peregrina Alexandra , Saramago Margarida , Viegas Sandra C. , Carvalho Sandra M. , Saraiva Lígia M. , Domingues Susana , Arraiano Cecília M. 
Published: October 2019

SummaryPseudomonas putida is a highly attractive production system for industrial needs. Modulation of gene expression is an urgent need to redesign P. putida metabolism for its improvement as biocatalyst at industrial level. We report the construction of a small RNA-based system with potential to be used for different purposes in synthetic biology. Due to their modular composition, design facilities and ability in tuning gene expression, sRNAs constitute a powerful tool in genetic and metabolic engineering. In the toolbox presented here, the synthetic sRNA is specifically directed to any region of a chosen target. The expression of the synthetic sRNAs is shown to differentially modulate the level of endogenous and reporter genes. The antisense interaction of the sRNA with the mRNA results in different outcomes. Depending on the particularity of each sRNA-target mRNA pair, we managed to demonstrate the duality of this system, able either to repress or overexpress a given gene. This system combines a high specificity with a wide applicability due to its ability to modulate the expression of virtually any given gene. By plugging-in and -out genetic circuits, this tailor-made regulatory system can be used to redesign P. putida metabolism, fulfilling an important industrial gap in synthetic biology.
FMRP Control of Ribosome Translocation Promotes Chromatin Modifications and Alternative Splicing of Neuronal Genes Linked to Autism
Authors: Shah Sneha , Molinaro Gemma , Liu Botao , Wang Ruijia , Huber Kimberly M. , Richter Joel D. 
Published: October 2019

SummarySilencing of FMR1 and loss of its gene product FMRP results in Fragile X Syndrome. FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1-deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wildtype tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes; and its loss results in decline of ribosome stalling on specific mRNAs. One such mRNA encodes SETD2, a lysine methyltransferase that catalyzes H3K36me3. ChIP-Seq demonstrates that loss of FMRP alters the deployment of this epigenetic mark on chromatin. H3K36me3 is associated with alternative pre-RNA processing, which we find occurs in an FMRP-dependent manner on transcripts linked to neural function and autism spectrum disorders.Highlights- Loss of FMRP results in decline of ribosome stalling on specific mRNAs (eg., SETD2)- Increased SETD2 protein levels alter H3K36me3 marks in FMRP deficient hippocampus- Genome-wide changes in mRNA alternative splicing occur in FMRP deficient hippocampus- H3K36me3 marks and alternative splicing changes occur on transcripts linked to autism