bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability and Control of Biomolecular Circuits through Structure
Authors: Xiao Fangzhou , Khammash Mustafa , Doyle John C. 
Published: November 2020

AbstractDue to omnipresent uncertainties and environmental disturbances, natural and engineered biological organisms face the challenging control problem of achieving robust performance using unreliable parts. The key to overcoming this challenge rests in identifying structures of biomolecular circuits that are largely invariant despite uncertainties, and building feedback control through such structures. In this work, we develop the tool of log derivatives to capture structures in how the production and degradation rates of molecules depend on concentrations of reactants. We show that log derivatives could establish stability of fixed points based on structure, despite large variations in rates and functional forms of models. Furthermore, we demonstrate how control objectives, such as robust perfect adaptation (i.e. step disturbance rejection), could be implemented through the structures captured. Due to the method’s simplicity, structural properties for analysis and design of biomolecular circuits can often be determined by a glance at the equations.
Age-related degradation of optic radiation white matter predicts visual, but not verbal executive functions
Authors: Webb Christina E. , Viera Perez Patricio M. , Hoagey David A. , Gonen Chen , Rodrigue Karen M. , Kennedy Kristen M. 
Published: November 2020

AbstractHealthy aging is accompanied by degraded white matter connectivity, which has been suggested to contribute to cognitive dysfunction observed in aging, especially in relation to fluid measures of cognition. Prior research linking white matter microstructure and cognition, however, has largely been limited to major association and heteromodal white matter tracts. The optic radiations (OR), which transfer visual sensory-perceptual information from thalamic lateral geniculate nucleus to primary visual cortex, are generally considered lower-level input-relay white matter tracts. However, the role of this prominent white-matter visual relay system in supporting higher-order cognition is understudied, especially in regard to healthy aging. The present study used deterministic tractography to isolate OR fractional anisotropy (FA) in 130 participants aged 20-94 to assess age effects on OR tract white matter. We also examined associations between age-related differences in the OR and cognitive domains involving visual processing speed, and visual- and non-visual executive function (EF). OR microstructure, as indexed by FA, exhibited a significant linear decrease across age. A significant interaction between age, FA, and cognitive domain on cognitive task performance indicated that in older age, more degraded OR white matter was associated with poorer visual EF, but no age-related association between FA in the OR and visual processing speed or verbal EF was observed. These findings suggest the optic radiations are not merely sensory-perceptual relays, but also influence higher-order visual cognition differentially with age.
Northward range expansion of the European green crabCarcinus maenasin the SW Atlantic: a synthesis after ~20 years of invasion history
Authors: Malvé Mariano E. , Rivadeneira Marcelo M. , Gordillo Sandra 
Published: November 2020

AbstractThis study aims at synthesizing the recent invasion history ofCarcinus maenasin the SW Atlantic (~20 years), particularly the northward expansion, based on available published papers, technical reports, and new field surveys. Our analyses extend the known distribution range northwards ca. 330 km. totaling ~1000 km along the Argentinean coast since its last detection in Nuevo Gulf in 2015. The expansion rate appeared to slow down during the last 15 years (from 115km/yr. to 30 km/yr.) as the species continues moving northwards into the transition zone between the Magellan and Argentinean biogeographic provinces (41°–43°S). In addition, a species distribution model (SDM) is provided at a much finer spatial resolution than previous studies, which accurately foresees suitable areas of invasion in the southern San Jorge Gulf, and predicts a hotspot of invasibility around 40°–33°S° if the invasion continues northward. Potential impacts ofC. maenason native species, particularly economically important oyster beds are discussed.
Streamlined and quantitative detection of chimerism in mouse tissue using digital PCR
Authors: Suchy Fabian P. , Nishimura Toshiya , Wilkinson Adam C. , Higuchi Maimi , Bhadury Joydeep , Nakauchi Hiromitsu 
Published: November 2020

ABSTRACTAnimal chimeras are widely used for biomedical discoveries, from developmental biology to cancer research. However, the accurate quantitation of mixed cell types in chimeric and mosaic tissues has challenges. Here, we have developed and characterized a droplet digital PCR single-nucleotide discrimination assay to detect chimerism among albino and non-albino mouse strains. In addition, we have validated that this assay is compatible with crude lysate from most organs, drastically streamlining sample preparation. This chimerism detection assay has many additional advantages over existing methods including its robust nature, minimal technical bias, and ability to report the total number of cells in a prepared sample. Importantly, the concepts developed and discussed here are readily adapted to other genomic loci to accurately measure mixed cell populations in any tissue.
Mechanistic inferences from analysis of measurements of protein phase transitions in live cells
Authors: Posey Ammon E. , Ruff Kiersten M. , Lalmansingh Jared M. , Kandola Tejbir S. , Lange Jeffrey J. , Halfmann Randal , Pappu Rohit V. 
Published: November 2020

AbstractThe combination of phase separation and disorder-to-order transitions can give rise to ordered, semi-crystalline fibrillar assemblies that underlie prion phenomena namely, the non-Mendelian transfer of information across cells. Recently, a method known as Distributed Amphifluoric Förster Resonance Energy Transfer (DAmFRET) was developed to study the convolution of phase separation and disorder-to-order transitions in live cells. In this assay, a protein of interest is expressed to a broad range of concentrations and the acquisition of local density and order, measured by changes in FRET, is used to map phase transitions for different proteins. The high-throughput nature of this assay affords the promise of uncovering sequence-to-phase behavior relationships in live cells. Here, we report the development of a supervised method to obtain automated and accurate classifications of phase transitions quantified using the DAmFRET assay. Systems that we classify as undergoing two-state discontinuous transitions are consistent with prion-like behaviors, although the converse is not always true. We uncover well-established and surprising new sequence features that contribute to two-state phase behavior of prion-like domains. Additionally, our method enables quantitative, comparative assessments of sequence-specific driving forces for phase transitions in live cells. Finally, we demonstrate that a modest augmentation of DAmFRET measurements, specifically time-dependent protein expression profiles, can allow one to apply classical nucleation theory to extract sequence-specific lower bounds on the probability of nucleating ordered assemblies. Taken together, our approaches lead to a useful analysis pipeline that enables the extraction of mechanistic inferences regarding phase transitions in live cells.
A Workflow of Integrated Resources to Catalyze Network Pharmacology Driven COVID-19 Research
Authors: Zahoránszky-Kőhalmi Gergely , Siramshetty Vishal B. , Kumar Praveen , Gurumurthy Manideep , Grillo Busola , Mathew Biju , Metaxatos Dimitrios , Backus Mark , Mierzwa Tim , Simon Reid , Grishagin Ivan , Brovold Laura , Mathé Ewy A. , Hall Matthew D. , Michael Samuel G. , Godfrey Alexander G. , Mestres Jordi , Jensen Lars J. , Oprea Tudor I. 
Published: November 2020

AbstractMotivationIn the event of an outbreak due to an emerging pathogen, time is of the essence to contain or to mitigate the spread of the disease. Drug repositioning is one of the strategies that has the potential to deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic has shown that integrating critical data resources to drive drug-repositioning studies, involving host-host, hostpathogen and drug-target interactions, remains a time-consuming effort that translates to a delay in the development and delivery of a life-saving therapy.ResultsHere, we describe a workflow we designed for a semi-automated integration of rapidly emerging datasets that can be generally adopted in a broad network pharmacology research setting. The workflow was used to construct a COVID-19 focused multimodal network that integrates 487 host-pathogen, 74,805 host-host protein and 1,265 drug-target interactions. The resultant Neo4j graph database named “Neo4COVID19” is accessible via a web interface and via API calls based on the Bolt protocol. We believe that our Neo4COVID19 database will be a valuable asset to the research community and will catalyze the discovery of therapeutics to fight COVID-19.Availabilityhttps://neo4covid19.ncats.io
Analysis of Genomes of Bacterial Isolates from Lameness Outbreaks in Broilers
Authors: Ekesi N. Simon , Dolka Beata , Alrubaye Adnan A.K. , Rhoads Douglas D. 
Published: November 2020

AbstractWe investigated lameness outbreaks at commercial broiler farms in Arkansas. From Bacterial Chondronecrosis with Osteomyelitis (BCO) lesions, we obtained different isolates of distinct bacterial species. Genome assemblies forEscherichia coliandStaphylococcus aureusisolates show that BCO-lameness pathogens on farms can differ significantly. Genomes assembled fromEscherichia coliisolates from three different farms were quite different from each other, and more similar to isolates from different hosts and geographical locations. The S aureus genomes were closely related to chicken isolates from Europe, and appear to have been restricted to chicken hosts for more than 40 years. Detailed analyses of genomes from this clade of chicken isolates with a sister clade of human isolates, suggests the acquisition of a particular pathogenicity island in the transition from human to chicken pathogen and that pathogenesis in chickens may depend on this mobile element. Phylogenomics is consistent with more frequent host shifts forE. coli, whileS. aureusappears to be highly host restricted. Isolate-specific genome characterizations will help further our understanding of the disease mechanisms and spread of BCO-lameness, a significant animal welfare issue.ImportanceDetailed inspection of the genome sequences of different bacterial species associated with causing lameness in broiler chickens reveals that one species,E. coli, appears to easily switch hosts from humans to chickens and other host species. Conversely, isolates ofS. aureusappear to be restricted to specific hosts. One potential mobile DNA element has been identified that may be critical for causing disease in chickens forS. aureus.
Rapid High Throughput Whole Genome Sequencing of SARS-CoV-2 by using One-step RT-PCR Amplification with Integrated Microfluidic System and Next-Gen Sequencing
Authors: Li Tao , Chung Hye Kyung , Pireku Papa K. , Beitzel Brett F. , Sanborn Mark A. , Tang Cynthia Y. , Hammer Richard , Ritter Detlef , Wan XiuFeng , Berry Irina Maljkovic , Hang Jun 
Published: November 2020

ABSTRACTThe long-lasting global COVID-19 pandemic demands timely genomic investigation of SARS-CoV-2 viruses. Here we report a simple and efficient workflow for whole genome sequencing utilizing one-step RT-PCR amplification on a microfluidic platform, followed by MiSeq amplicon sequencing. The method uses Fluidigm IFC and instruments to amplify 48 samples with 39 pairs of primers in a single step. Application of this method on RNA samples from both viral isolate and clinical specimens demonstrate robustness and efficiency of this method in obtaining the full genome sequence of SARS-CoV-2.
Characteristics of three different chemiluminescence assays for testing for SARS-CoV-2 antibodies
Authors: Weber Myriam C. , Risch Martin , Thiel Sarah L. , Grossmann Kirsten , Nigg Susanne , Wohlwend Nadia , Lung Thomas , Hillmann Dorothea , Ritzler Michael , Ferrara Francesca , Bigler Susanna , Egli Konrad , Bodmer Thomas , Imperiali Mauro , Salimi Yacir , Fleisch Felix , Cusini Alexia , Heer Sonja , Renz Harald , Paprotny Matthias , Kohler Philipp , Vernazza Pietro , Risch Lorenz , Kahlert Christian R. 
Published: November 2020

AbstractSeveral tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multi-group study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 (n=145), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e. healthy blood donors, n=191, and healthcare workers, n=1002). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of Epstein–Barr virus (EBV) (n=9), cytomegalovirus (CMV) (n=7) and endemic common cold coronavirus infections (n=12) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers’ cut-offs, the sensitivities were 90%, 95% confidence interval,[84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8](CMIA) 99.7% [99.3,99,9] (LIA) and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers’ cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers’ cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.
A Randomized Controlled Trial to Increase Cancer Screening and Reduce Depression among Low-Income Women
Authors: Tobin Jonathan N. , Weiss Elisa S. , Cassells Andrea , Lin TJ , Carrozzi Gianni , Barsanti Franco , Morales Alejandra , Mailing Alison , Espejo Maria , Gilbert Erica , Casano Louann , O’Hara-Cicero Ellen , Weed John , Dietrich Allen J. 
Published: November 2020

AbstractBackgroundWomen from low-income, racial/ethnic minority backgrounds receive fewer cancer screenings than other womenandhave higher rates of depression, which can interfere with cancer screening participation.ObjectiveAssess the comparative effectiveness of two interventions to improve breast, cervical, and colorectal cancer screening and reduce depression among underserved women with depressive symptoms.DesignRandomized comparative effectiveness trialSettingSix Federally Qualified Health CentersParticipantsN=757, 50-64 years with depression symptoms and overdue for cancer screening.InterventionsParticipants were randomized to collaborative depression care plus cancer screening intervention (Collaborative Care Intervention, CCI) or cancer screening intervention alone (Prevention Care Management, PCM). Both of these evidence-based, telephone interventions were delivered in English or Spanish, for up to 12 months, by care managers.MeasurementsElectronic Health Records provided cancer screening data (primary outcome). PHQ-9 measured depression at study entry (T0), 6- and 12-months post-baseline (T1 and T2, respectively; secondary outcome).ResultsAnalyses revealed statistically significant increases in up-to-date status for all cancer screenings; depression improved in both intervention groups. There were no statistically significant differences between the two interventions in improving cancer screening rates or reducing depression.LimitationsDepressive symptom improvement may be explained by typical symptom remission. The study duration (12-months) was insufficient to evaluate intervention effects on long-term cancer screening behavior and depression. This study was not powered for site-level analysis.ConclusionsCCI and PCM both improved breast, cervical, and colorectal cancer screening and depression in clinical settings in underserved communities, however neither intervention showed an advantage in outcomes. Decisions about which approach to implement may depend on the nature of the practice and alignment of the interventions with other ongoing priorities and resources.Funding sourceThis study was funded by Patient Centered Outcomes Research Institute (PCORI) (IH-12-11-4522) with additional infrastructure support from Agency for Healthcare Research and Quality (AHRQ) (5P30-HS-021667).
Relationship of sleep homeostasis to seizures and cognition in children with focal epilepsy
Authors: Eriksson Maria H , Baldeweg Torsten , Pressler Ronit , Boyd Stewart G , Huber Reto , Cross J Helen , Bölsterli Bigna K , Chan Samantha YS 
Published: November 2020

AbstractObjectiveSleep disruption and cognitive impairment are important co-morbidities in childhood epilepsy, yet a mechanistic link has not been substantiated. Slow wave activity during sleep and its homeostatic decrease across the night is associated with synaptic renormalisation, and shows maturational changes over the course of childhood. Here, we aimed to investigate the effect of epilepsy on sleep homeostasis in the developing brain.MethodsWe examined the relationship of sleep homeostasis as reflected in slow wave activity to seizures, cognition and behaviour, comparing 22 children (aged 6 to 16 years) with focal epilepsy to 21 age-matched healthy controls. Participants underwent overnight sleep EEG and IQ testing and performed memory consolidation tasks. Their parents completed standard behavioural questionnaires.ResultsChildren with epilepsy had lower slow wave activity at the start of non-rapid eye movement (NREM) sleep, though similar overnight decline and slow wave activity in the final hour of NREM sleep. Both groups displayed an antero-posterior shift in peak slow wave activity overnight, though individual patients showed persistent local increases at scalp locations matching those of focal interictal discharges. Patients who had seizures during their admission had lower early-night slow wave activity, the group without seizures showing similar activity to controls. We found a positive correlation between full scale IQ and early-night slow wave activity in patients but not controls.InterpretationReduced early night slow wave activity in children with focal epilepsies is correlated with lower cognitive ability and more seizures and may reflect a reduction in learning-related synaptic potentiation.
Transcription and splicing dynamics during early Drosophila development
Authors: Prudêncio Pedro , Savisaar Rosina , Rebelo Kenny , Martinho Rui Gonçalo , Carmo-Fonseca Maria 
Published: November 2020

ABSTRACTWidespread co-transcriptional splicing has been demonstrated from yeast to human. However, most studies to date addressing the kinetics of splicing relative to transcription used either Saccharomyces cerevisiae or metazoan cultured cell lines. Here, we adapted native elongating transcript sequencing technology (NET-seq) to measure co-transcriptional splicing dynamics during the early developmental stages of Drosophila melanogaster embryos. Our results reveal the position of RNA polymerase II (Pol II) when both canonical and recursive splicing occur. We found heterogeneity in splicing dynamics, with some RNAs spliced immediately after intron transcription, whereas for other transcripts no splicing was observed over the first 100 nucleotides of the downstream exon. Introns that show splicing completion before Pol II has reached the end of the downstream exon are necessarily intron-defined. We studied the splicing dynamics of both nascent pre-mRNAs transcribed in the early embryo, which have few and short introns, as well as pre-mRNAs transcribed later in embryonic development, which contain multiple long introns. As expected, we found a relationship between the proportion of spliced reads and intron size. However, intron definition was observed at all intron sizes. We further observed that genes transcribed in the early embryo tend to be isolated in the genome whereas genes transcribed later are often overlapped by a neighboring convergent gene. In isolated genes, transcription termination occurred soon after the polyadenylation site, while in overlapped genes Pol II persisted associated with the DNA template after cleavage and polyadenylation of the nascent transcript. Taken together, our data unravels novel dynamic features of Pol II transcription and splicing in the developing Drosophila embryo.
Spatially resolved transcriptomics reveals the architecture of the tumor/microenvironment interface
Authors: Hunter Miranda V. , Moncada Reuben , Weiss Joshua M. , Yanai Itai , White Richard M. 
Published: November 2020

SUMMARYDuring tumor progression, cancer cells come into contact with novel non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct “interface” cell state where the tumor contacts neighboring tissues. This interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes, and cilia proteins are enriched only where the tumor contacts the microenvironment. Cilia gene expression is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. An ETS-driven interface is conserved in human patient samples, suggesting it is a conserved feature of human melanoma. Our results demonstrate the power of spatially resolved transcriptomics in uncovering mechanisms that allow tumors to adapt to new environments.
Mevalonate pathway-mediated ER homeostasis is required for haploid stability in human somatic cells
Authors: Yaguchi Kan , Sato Kimino , Yoshizawa Koya , Banhegyi Gabor , Margittai Eva , Uehara Ryota 
Published: November 2020

AbstractThe somatic haploidy is unstable in diplontic animals, but cellular processes determining haploid stability remain elusive. Here, we found that inhibition of mevalonate pathway by pitavastatin, a widely used cholesterol-lowering drug, drastically destabilized the haploid state in HAP1 cells. Interestingly, cholesterol supplementation did not restore haploid stability in pitavastatin-treated cells, and cholesterol inhibitor U18666A did not phenocopy haploid destabilization. These results ruled out the involvement of cholesterol in haploid stability. Besides cholesterol perturbation, pitavastatin induced endoplasmic reticulum (ER) stress, the suppression of which by a chemical chaperon significantly restored haploid stability in pitavastatin-treated cells. Our data demonstrate the involvement of the mevalonate pathway in the stability of the haploid state in human somatic cells through managing ER stress, highlighting a novel link between ploidy and ER homeostatic control.