bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting functional long non-coding RNAs validated by low throughput experiments
Authors: Zhou Bailing , Yang Yuedong , Zhan Jian , Dou Xianghua , Wang Jihua , Zhou Yaoqi 
Published: May 2019

ABSTRACTHigh-throughput techniques have uncovered hundreds and thousands of long non-coding RNAs (lncRNAs). Among them, only a small fraction has experimentally validated functions (EVlncRNAs) by low-throughput methods. What fraction of lncRNAs from high-throughput experiments (HTlncRNAs) is truly functional is an active subject of debate. Here, we developed the first method to distinguish EVlncRNAs from HTlncRNAs and mRNAs by using Support Vector Machines and found that EVlncRNAs can be well separated from HTlncRNAs and mRNAs with 0.6 for Matthews correlation coefficient, 64% for sensitivity, and 81% for precision for the independent human test set. The most discriminative features are related to sequence conservations at RNA (for separating from HTlncRNAs) and protein (for separating from mRNA) levels. The method is found to be robust as the human-RNA-trained model is applicable to independent mouse RNAs with similar accuracy and to a lesser extent to plant RNAs. The method can recover newly discovered EVlncRNAs with high sensitivity. Its application to randomly selected 2000 human HTlncRNAs indicates that a large number of functional lncRNAs are waiting to be validated. The method is expected to speed up and reduce the cost of the discovery by prioritizing potentially functional lncRNAs prior to experimental validation. EVlncRNA-pred is available as a web server at http://biophy.dzu.edu.cn/lncrnapred/index.html. All datasets used in this study can be obtained from the same website.
Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study
Authors: Tripoli Giada , Quattrone Diego , Ferraro Laura , Gayer-Anderson Charlotte , Rodriguez Victoria , Cascia Caterina La , Barbera Daniele La , Sartorio Crocettarachele , Tarricone Ilaria , Berardi Domenico , Szöke Andrei , Arango Celso , Tortelli Andrea , Llorca Pierre-Michel , de Haan Lieuwe , Velthorst Eva , Bobes Julio , Bernardo Miguel , Sanjuán Julio , Santos Jose Luis , Arrojo Manuel , Del-Ben Cristina Marta , Menezes Paulo Rossi , Selten Jean-Paul ,   EU-GEI WP2 Group, Jones Peter B , Richards Alex , O’Donovan Michael , Rutten Bart PF , van Os Jim , Morgan Craig , Sham Pak C , Murray Robin M , Murray Graham K , Forti Marta Di 
Published: May 2019

AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia Polygenic Risk Score (SZ PRS) was non-significantly associated with a higher number of beads drawn (B= 0.47, 95% CI −0.21 to 1.16, p=0.17); whereas IQ PRS (B=0.51, 95% CI 0.25 to 0.76, p<0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with higher level of psychotic-like experiences (PLE) in controls, including after controlling for IQ (B= −1.7, 95% CI −2.8 to −0.5, p=0.006), but did not relate to delusions in patients.Conclusionsthe JTC reasoning bias in psychosis is not a specific cognitive deficit but is rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to psychotic-like experiences, independent of IQ. The work has potential to inform interventions targeting cognitive biases in early psychosis.
Nucleosomal DNA dynamics mediate Oct4 pioneer factor binding
Authors: Huertas Jan , MacCarthy Caitlin M. , Schöler Hans , Cojocaru Vlad 
Published: May 2019

AbstractTranscription factor (TF) proteins bind to DNA to regulate gene expression. Normally, accessibility to DNA is required for their function. However, in the nucleus the DNA is often inaccessible, wrapped around histone proteins in nucleosomes forming the chromatin. Pioneer TFs are thought to induce chromatin opening by recognizing their DNA binding sites on nucleosomes. For example, Oct4, a master regulator and inducer of stem cell pluripotency, binds to DNA in nucleosomes in a sequence specific manner. Here we reveal the structural dynamics of nucleosomes that mediate Oct4 binding. Nucleosome mobility and the amplitude of nucleosome motions such as breathing and twisting correlate with the number of Oct4 binding sites available. Moreover, the regions around the binding sites display higher local mobility. Probing different structures of Oct4-nucleosome complexes, we show that alternative configurations display stable protein-DNA interactions and are compatible with the DNA curvature and DNA-histone interactions.
Dysregulated Alternative Splicing Landscape Identifies Intron Retention as a Hallmark and Spliceosome as a Therapeutic Vulnerability in Aggressive Prostate Cancer
Authors: Zhang Dingxiao , Hu Qiang , Ji Yibing , Chao Hsueh-Ping , Tracz Amanda , Kirk Jason , Buonamici Silvia , Zhu Ping , Wang Jianmin , Liu Song , Tang Dean G. 
Published: May 2019

ABSTRACTDysregulation of mRNA alternative splicing (AS) has been implicated in development and progression of hematological malignancies. Here we describe the first comprehensive AS landscape in the spectrum of human prostate cancer (PCa) development, progression and therapy resistance. We find that the severity of splicing dysregulation correlates with disease progression and establish intron retention (IR) as a hallmark of PCa stemness and aggressiveness. Systematic interrogation of 274 splicing-regulatory genes (SRGs) uncovers prevalent SRG mutations associated with, mainly, copy number variations leading to mis-expression of ~68% of SRGs during PCa evolution. Consequently, we identify many SRGs as prognostic markers associated with splicing disruption and patient outcome. Interestingly, androgen receptor (AR) controls a splicing program distinct from its transcriptional regulation. The spliceosome modulator, E7107, reverses cancer aggressiveness and abolishes the growth of castration-resistant PCa (CRPC) models. Altogether, we establish aberrant AS landscape caused by dysregulated SRGs as a novel therapeutic vulnerability for CRPC.Statement of significanceWe present the first comprehensive AS landscape during PCa evolution and link genomic and transcriptional alterations in SRGs to global splicing dysregulation. AR regulates splicing in pri-PCa and CRPC distinct from its transcriptional regulation. Intron retention is a hallmark for and spliceosome represents a therapeutic vulnerability in aggressive PCa.
Sleep deprivation rapidly upregulates serotonin 2A receptor expression via the immediate early gene Egr3
Authors: Zhao X. , Meyers K. T. , McBride A. , Marballi K. K. , Maple A. M. , Beck K. L. , Kang P. , Palner M. , Overgaard A. , Knudsen G. M. , Gallitano A. L. 
Published: May 2019

AbstractSerotonin 2A receptors (5-HT2ARs) mediate the effects of hallucinogenic drugs and antipsychotic medications, and are reduced in schizophrenia patients’ brains. However, the mechanisms that regulate 5-HT2AR expression remain poorly understood. We show that an environmental stimulus, sleep deprivation, upregulates 5-HT2ARs in the mouse frontal cortex (FC) in just 6-8 hours. This induction requires the immediate early gene transcription factor early growth response 3 (Egr3). Further, EGR3 binds to the Htr2a promoter in the FC in vivo, and drives reporter construct expression in vitro via two Htr2a promoter binding sites. These findings suggest that EGR3 directly regulates FC Htr2a expression in response to physiologic stimuli, providing a mechanism by which environment rapidly alters levels of a brain receptor that mediates symptoms, and treatment, of mental illness.One Sentence SummaryJust 6-8 hours of sleep deprivation upregulates brain levels of the receptor that mediates the response to hallucinogens.
Real Time Ultrasound Molecular Imaging of Prostate Cancer with PSMA-targeted Nanobubbles
Authors: Perera Reshani , de Leon Al , Wang Xinning , Wang Yu , Ramamurthy Gopal , Peiris Pubudu , Abenojar Eric , Basilion James P. , Exner Agata A. 
Published: May 2019

AbstractContrast-enhanced ultrasound with microbubbles has shown promise in detection of prostate cancer (PCa), but sensitivity and specificity of detection remain challenging. Targeted nanoscale contrast agents with improved capability to accumulate in tumors may result in prolonged signal enhancement and improved detection of PCa with ultrasound. Here we report on a new nanobubble contrast agent that specifically targets prostate specific membrane antigen (PSMA) overexpressed in most prostate tumors. The PSMA-targeted bubbles (PSMA-NB) were utilized to simultaneously image dual flank PCa tumors (PSMA-positive PC3pip and PSMA-negative PC3flu) to examine whether the biomarker can be successfully detected and imaged using this probe in a mouse model. Results demonstrate that active targeting of NBs to PSMA rapidly and selectively enhances tumor accumulation and is critical for tumor retention of the contrast agent. Importantly, these processes could be visualized and quantified, in real time, with standard clinical ultrasound. Such demonstration of the immense yet underutilized potential of ultrasound in the area of molecular imaging can open the door to future opportunities for improving sensitivity and specificity of cancer detection using parametric NB-enhanced ultrasound imaging.
Reciprocal connectivity between secondary auditory cortical field and amygdala in mice
Authors: Tsukano Hiroaki , Hou Xubin , Horie Masao , Kitaura Hiroki , Nishio Nana , Hishida Ryuichi , Takahashi Kuniyuki , Kakita Akiyoshi , Takebayashi Hirohide , Sugiyama Sayaka , Shibuki Katsuei 
Published: May 2019

AbstractRecent studies have examined the feedback pathway from the amygdala to the auditory cortex in conjunction with the feedforward pathway from the auditory cortex to the amygdala. However, these connections have not been fully characterized. Here, to visualize the comprehensive connectivity between the auditory cortex and amygdala, we injected cholera toxin subunit b (CTB), a bidirectional tracer, into multiple subfields in the mouse auditory cortex after identifying the location of these subfields using flavoprotein fluorescence imaging. After injecting CTB into the secondary auditory field (A2), we found densely innervated CTB-positive axon terminals that were mainly located in the lateral amygdala (La), and slight innervations in other divisions such as the basal amygdala. Moreover, we found a large number of retrogradely-stained CTB-positive neurons in La after injecting CTB into A2. When injecting CTB into the primary auditory cortex (A1), a small number of CTB-positive neurons and axons were visualized in the amygdala. Finally, we found a near complete absence of connections between the other auditory cortical fields and the amygdala. These data suggest that reciprocal connections between A2 and La are main conduits for communication between the auditory cortex and amygdala in mice.
Dsuite - fast D-statistics and related admixture evidence from VCF files
Authors: Malinsky Milan , Matschiner Michael , Svardal Hannes 
Published: May 2019

AbstractPatterson’s D, also known as the ABBA-BABA statistic, and related statistics such as the f4-ratio, are commonly used to assess evidence of gene flow between populations or closely related species. Currently available implementations require custom file formats and are impractical to evaluate all gene flow hypotheses across datasets with many populations or species.Dsuite is a fast C++ implementation, allowing genome scale calculations of the D and f4-ratio statistics across all combinations of tens or hundreds of populations or species directly from a variant call format (VCF) file. Furthermore, the program can provide evidence of whether introgression is confined to specific loci and aid in interpretation of a system of f4-ratio results by implementing the ‘f-branch’ method.Dsuite is available at https://github.com/millanek/Dsuite, is straightforward to use, substantially more computationally efficient than other comparable programs, and presents a novel suite of tools and statistics, including some not previously available in any software package.Thus, Dsuite facilitates assessment of evidence for gene flow, especially across large genomic datasets.
Automated data-intensive forecasting of plant phenology throughout the United States
Authors: Taylor Shawn D. , White Ethan P. 
Published: May 2019

AbstractPhenology - the timing of cyclical and seasonal natural phenomena such as flowering and leaf out - is an integral part of ecological systems with impacts on human activities like environmental management, tourism, and agriculture. As a result, there are numerous potential applications for actionable predictions of when phenological events will occur. However, despite the availability of phenological data with large spatial, temporal, and taxonomic extents, and numerous phenology models, there has been no automated species-level forecasts of plant phenology. This is due in part to the challenges of building a system that integrates large volumes of climate observations and forecasts, uses that data to fit models and make predictions for large numbers of species, and consistently disseminates the results of these forecasts in interpretable ways. Here we describe a new near-term phenology forecasting system that makes predictions for the timing of budburst, flowers, ripe fruit, and fall colors for 78 species across the United States up to 6 months in advance and is updated every four days. We use the lessons learned in developing this system to provide guidance developing large-scale near-term ecological forecast systems more generally, to help advance the use of automated forecasting in ecology.
Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples
Authors: Butt Salman L. , Erwood Eric C. , Zhang Jian , Sellers Holly S. , Young Kelsey , Lahmers Kevin K. , Stanton James B. 
Published: May 2019

AbstractInfectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of infectious bronchitis is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. While serotyping by definition requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV and it is inefficient at detecting mixed isolates. This paper describes a MinION-based AmpSeq method that genetically typed IBV from clinical samples, including samples with multiple isolates. Total RNA was extracted from fifteen tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer’s instructions into a 1D MinION sequencing library, and sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in three of five samples containing two IBV lineages. Additionally, one sample contained three IBV lineages, and AmpSeq accurately detected two of the three. Strain identification, including detection of different strains from the same lineage, was also possible with this AmpSeq method. The results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.
CRISPR editing of sftb-1/SF3B1 in C. elegans allows the identification of synthetic interactions with cancer-related mutations and the chemical inhibition of splicing
Authors: Serrat Xènia , Kukhtar Dmytro , Cornes Eric , Esteve-Codina Anna , Benlloch Helena , Cecere Germano , Cerón Julián 
Published: May 2019

ABSTRACTSF3B1 is the most frequently mutated splicing factor in cancer. Mutations in SF3B1 confer growth advantages to cancer cells but they may also confer vulnerabilities that can be therapeutically targeted. In contrast to other animal models, SF3B1 cancer mutations can be maintained in homozygosis in C. elegans, allowing synthetic lethal screens with a homogeneous population of animals. These mutations cause alternative splicing (AS) defects in C. elegans, as it occurs in SF3B1-mutated human cells. In a screen, we identified RNAi of U2 snRNP components that cause synthetic lethality with sftb-1/SF3B1 mutations. We also detected synthetic interactions between sftb-1 mutants and cancer-related mutations in uaf-2/U2AF1 or rsp-4/SRSF2, demonstrating that this model can identify interactions between mutations that are mutually exclusive in human tumors. Finally, we have edited an SFTB-1 domain to sensitize C. elegans to the splicing inhibitor pladienolide B. Thus, we have established a multicellular model for SF3B1 mutations amenable for high-throughput genetic and chemical screens.
Complex community-wide consequences of consumer sexual dimorphism
Authors: De Lisle Stephen P. , Schrieber Sebastian J. , Bolnick Daniel I. 
Published: May 2019

AbstractSexual dimorphism is a ubiquitous source of within-species variation, yet the communitylevel consequences of sex differences remain poorly understood. Here, we analyze a bitrophic model of two competing resource species and a sexually-reproducing consumer species. We show that consumer sex differences in resource acquisition can have striking consequences for consumer-resource coexistence, abundance, and dynamics. Under both direct interspecific competition and apparent competition between two resource species, sexual dimorphism in consumers’ attack rates can mediate coexistence of the resource species, while in other cases can lead to exclusion when stable coexistence is typically expected. Slight sex differences in total resource acquisition also can reverse competitive outcomes and lead to density cycles. These effects are expected whenever both consumer sexes require different amounts or types of resources to reproduce. Our results suggest that consumer sexual dimorphism, which is common, has wide-reaching implications for the assembly and dynamics of natural communities.Statement of authorshipDB SD and SJS designed the study, SJS performed the mathematical analysis, SD performed the simulations and drafted the manuscript. All authors revised the manuscript.Data accessibility statementNo data is used
How do red-eyed treefrog embryos sense motion in predator attacks? Assessing the role of vestibular mechanoreception
Authors: Jung Julie , Kim Su J. , Pérez Arias Sonia M. , McDaniel James G. , Warkentin Karen M. 
Published: May 2019

ABSTRACTThe widespread ability to alter hatching timing in response to environmental cues can serve as a defense against threats to eggs. Arboreal embryos of red-eyed treefrogs, Agalychnis callidryas, hatch up to 30% prematurely to escape predation. This escape-hatching response is cued by physical disturbance of eggs during attacks, including vibrations or motion, and thus depends critically on mechanosensory ability. Predator-induced hatching appears later in development than flooding-induced, hypoxia-cued hatching; thus, its onset is not constrained by the development of hatching ability. It may, instead, reflect the development of mechanosensor function. We hypothesize that vestibular mechanoreception mediates escape-hatching in snake attacks, and that the developmental period when hatching-competent embryos fail to flee from snakes reflects a sensory constraint. We assessed the ontogenetic congruence of escape-hatching responses and an indicator of vestibular function, the vestibulo-ocular reflex (VOR), in three ways. First, we measured VOR in two developmental series of embryos 3–7 days old to compare with the published ontogeny of escape success in attacks. Second, during the period of greatest variation in VOR and escape success, we compared hatching responses and VOR across sibships. Finally, in developmental series, we compared the response of individual embryos to a simulated attack cue with their VOR. The onset of VOR and hatching responses were largely concurrent at all three scales. Moreover, latency to hatch in simulated attacks decreased with increasing VOR. These results are consistent with a key role of the vestibular system in the escape-hatching response of A. callidryas embryos to attacks.Red-eyed treefrogs’ hatching responses to predator attacks, vibration playbacks, and egg-jiggling appear when vestibular function develops. Ear development may be a key limiting factor in the onset of mechanosensory-cued hatching.
CLASP2 lattice-binding near microtubule plus ends stabilizes kinetochore attachments
Authors: Girão Hugo , Okada Naoyuki , Figueiredo Ana C. , Garcia Zaira , Moutinho-Santos Tatiana , Azevedo Jorge , Macedo-Ribeiro Sandra , Hayashi Ikuko , Maiato Helder 
Published: May 2019

AbstractThe fine regulation of kinetochore microtubule dynamics during mitosis ensures proper chromosome segregation by promoting error correction and spindle assembly checkpoint (SAC) satisfaction. CLASPs are widely conserved microtubule plus-end-tracking proteins that regulate microtubule dynamics throughout the cell cycle and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore microtubule dynamics, but the underlying molecular mechanism remains unknown. Here we found that human CLASP2 can dimerize through its C-terminal kinetochore-targeting domain, but kinetochore localization was independent of dimerization. CLASP2 kinetochore localization, microtubule plus-end-tracking and microtubule lattice binding through TOG2 and TOG3 (but not TOG1) domains, independently sustained normal spindle length, timely SAC satisfaction, chromosome congression and faithful segregation. Measurements of kinetochore microtubule half-life in living cells expressing RNAi-resistant mutants revealed that CLASP2 kinetochore localization, microtubule plus-end-tracking and lattice binding cooperatively modulate kinetochore microtubule stability during mitosis. Thus, CLASP2 regulates kinetochore microtubule dynamics by integrating distinctive microtubule-binding properties at the kinetochore-microtubule interface to ensure chromosome segregation fidelity.