bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulated immunity in SARS-CoV-2 infected pregnant women
Authors: Sherer Morgan L. , Lei Jun , Creisher Patrick , Jang Minyoung , Reddy Ramya , Voegtline Kristin , Olson Sarah , Littlefield Kirsten , Park Han-Sol , Ursin Rebecca L. , Ganesan Abhinaya , Boyer Theresa , Brown Diane M. , Walch Samantha N. , Antar Annukka A. R. , Manabe Yukari C. , Jones-Beatty Kimberly , Golden William Christopher , Satin Andrew J. , Sheffield Jeanne S. , Pekosz Andrew , Klein Sabra L. , Burd Irina 
Published: November 2020

AbstractImportanceThe effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated.ObjectiveTo assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women.DesignImmune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood.SettingJohns Hopkins Hospital (JHH)ParticipantsPregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study.ExposuresSARS-CoV-2Main Outcomes and MeasuresParticipant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression.ResultsSARS-COV-2 positive pregnant women expressed more IL1β, but not IL6, in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy.Conclusions and RelevanceSARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.
Molecular and spectroscopic characterization of green and red cyanine fluorophores from the Alexa Fluor and AF series
Authors: Gebhardt Christian , Lehmann Martin , Reif Maria M. , Zacharias Martin , Cordes Thorben 
Published: November 2020

AbstractThe use of fluorescence techniques has had an enormous impact on various research fields including imaging, biochemical assays, DNA-sequencing and medical technologies. This has been facilitated by the availability of numerous commercial dyes, but often information about the chemical structures of dyes (and their linkers) are a well-kept secret. This can lead to problems for applications where a knowledge of the dye structure is necessary to predict (unwanted) dye-target interactions, or to establish structural models of the dye-target complex. Using a combination of spectroscopy, mass spectrometry and molecular dynamics simulations, we here investigate the molecular structures and spectroscopic properties of dyes from the Alexa Fluor (Alexa Fluor 555 and 647) and AF series (AF555, AF647, AFD647). Based on available data and published structures of the AF and Cy dyes, we present two possible structures for Alexa Fluor 555. We also resolve conflicting reports on the linker composition of Alexa Fluor 647. A comprehensive comparison between Alexa Fluor and AF dyes by continuous-wave absorption and emission spectroscopy, quantum yield determination, fluorescence lifetime and anisotropy spectroscopy of free and protein-attached dyes, supports the suggestion that the Alexa Fluor and AF dyes have a high degree of structural similarity. In addition, we compared Alexa Fluor 555 and Alexa Fluor 647 to their structural homologs AF555 and AF(D)647 in single-molecule FRET applications. Both pairs showed excellent performance in solution-based smFRET experiments using alternating laser excitation demonstrating that the AF-fluorophores are an attractive alternative to Alexa- and Cy-dyes for smFRET studies, and suggesting their usefulness for other fluorescence applications.
In silicoinvestigation ofAedes aegyptimale-determining factor (NIX): RNA recognition motif-3, structural model and selective nucleic acid binding mode
Authors: Coronado Monika A. , Olivier Danilo S. , Borsatto Kelly C. , Amaral Marcos S. , Arni Raghuvir K. , Eberle Raphael J. 
Published: November 2020

AbstractMosquito borne viruses and their corresponding human infections have a fast growing impact on worldwide public health systems; in particular,Aedes aegyptiandAedes albopictusare transmitting these viruses. Only female mosquitoes bite and spread diseases. Male development inA. aegyptiis initiated by male determining factors. These factors are potential candidates for the implementation of vector control strategies. Where at an early stage in gender development female mosquitoes are converted into harmless males. Among these factors, a novel gene, NIX, has been identified that shares moderate identity with transformer-2, one of the key sex-determination genes inDrosophila melanogaster. Hall et al. 2015 described two RNA recognition motifs (RRMs) in the NIX sequence, but a UniProt database search showed thatA. aegyptiNIX contains three RNA RRM. A homology model of NIX_RRM-3 was generated to investigate the interaction with RNA using molecular dynamics simulations. The sequence AGACGU was the most interesting result. During the binding process A1, G2 and G5 adopt an unusualsynconformation. The results let assume that the C-terminus of NIX_RRM-3 is involved in the recognition process of the target RNA motif (e.g. AG) and controls the interaction between target RNA andA. aegyptiNIX.
Synaptic plasticity regulated by phosphorylation of PSD-95 Serine 73 in dorsal CA1 is required for contextual fear extinction
Authors: Ziółkowska Magdalena , Borczyk Malgorzata , Nowacka Agata , Nalberczak-Skóra Maria , Śliwińska Małgorzata Alicja , Robacha Magdalena , Łukasiewicz Kacper , Cały Anna , Skonieczna Edyta , Tomaszewski Kamil F. , Wójtowicz Tomasz , Włodarczyk Jakub , Bernaś Tytus , Salamian Ahmad , Radwanska Kasia 
Published: November 2020

ABSTRACTThe ability to extinguish fearful memories is essential for survival. Accumulating data indicate that the dorsal CA1 area (dCA1) contributes to this process. However, the cellular and molecular basis of fear memory extinction remains poorly understood. Postsynaptic density protein 95 (PSD-95) regulates the structure and function of glutamatergic synapses. Here, using dCA1-targeted genetic and chemogenetic manipulationsin vivocombined with PSD-95 immunostaining and 3D electron microscopyex vivo, we demonstrate that phosphorylation of PSD-95 at serine 73 PSD-95(S73) is necessary for contextual fear extinction-induced expression of PSD-95 and synaptic plasticity. Moreover, PSD-95(S73) phosphorylation is not necessary for fear memory formation and recall but is required for extinction of contextual fear. Overall, our data shows how PSD-95-dependent synaptic plasticity in the hippocampus contributes to the persistence of fear memories.
SMC Complexes Are Guarded by the SUMO Protease Ulp2 Against SUMO-Chain-Mediated Turnover
Authors: Psakhye Ivan , Branzei Dana 
Published: November 2020

ABSTRACTStructural maintenance of chromosomes (SMC) complexes, cohesin, condensin and Smc5/6, are essential for viability and participate in multiple processes, including sister chromatid cohesion, chromosome condensation, and DNA repair. Here we show that SUMO chains target all three SMC complexes and are antagonized by the SUMO protease Ulp2 to prevent their turnover. We uncover that the essential role of the cohesin-associated subunit Pds5 is to counteract SUMO chains jointly with Ulp2. Importantly, fusion of Ulp2 to kleisin Scc1 supports viability ofPDS5null cells and protects cohesin from proteasomal degradation mediated by the SUMO-targeted ubiquitin ligase Slx5/Slx8. The lethality ofPDS5deleted cells can also be bypassed by simultaneous loss of the PCNA unloader, Elg1, and the cohesin releaser, Wpl1, but only when Ulp2 is functional. Condensin and Smc5/6 complex are similarly guarded by Ulp2 against unscheduled SUMO-chain assembly, which we propose to time the availability of SMC complexes on chromatin.
Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures
Authors: Shimoda Yoshiteru , Leite Marco , Graham Robert T , Marvin Jonathan S , Hasseman Jeremy , Kolb Ilya , Looger Loren L , Magloire Vincent , Kullmann Dimitri M 
Published: November 2020

AbstractFocal epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood. We used fluorescent glutamate and GABA sensors in an awake rodent model of neocortical seizures to resolve the spatiotemporal evolution of both neurotransmitters in the extracellular space. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagated centrifugally. GABA transients lasted longer than glutamate transients and were maximal ∼1.5 mm from the focus where they propagated centripetally. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing seizures to escape from local inhibitory restraint.
Design of intrinsically disordered proteins that undergo phase transitions with lower critical solution temperatures
Authors: Zeng Xiangze , Liu Chengwen , Fossat Martin J. , Ren Pengyu , Chilkoti Ashutosh , Pappu Rohit V. 
Published: November 2020

AbstractMany naturally occurring elastomers are intrinsically disordered proteins (IDPs) built up of repeating units and they can demonstrate two types of thermoresponsive phase behavior. Systems characterized by lower critical solution temperatures (LCST) undergo phase separation above the LCST whereas systems characterized by upper critical solution temperatures (UCST) undergo phase separation below the UCST. There is congruence between thermoresponsive coil-globule transitions and phase behavior whereby the theta temperatures above or below which the IDPs transition from coils to globules serve as useful proxies for the LCST / UCST values. This implies that one can design sequences with desired values for the theta temperature with either increasing or decreasing radii of gyration above the theta temperature. Here, we show that the Monte Carlo simulations performed in the so-called intrinsic solvation (IS) limit version of the temperature-dependent the ABSINTH (self-Assembly of Biomolecules Studied by an Implicit, Novel, Tunable Hamiltonian) implicit solvation model, yields a useful heuristic for discriminating between sequences with known LCST versus UCST phase behavior. Accordingly, we use this heuristic in a supervised approach, integrate it with a genetic algorithm, combine this with IS limit simulations, and demonstrate that novel sequences can be designed with LCST phase behavior. These calculations are aided by direct estimates of temperature dependent free energies of solvation for model compounds that are derived using the polarizable AMOEBA (atomic multipole optimized energetics for biomolecular applications) forcefield. To demonstrate the validity of our designs, we calculate coil-globule transition profiles using the full ABSINTH model and combine these with Gaussian Cluster Theory calculations to establish the LCST phase behavior of designed IDPs.
Playbacks of Food-associated Calls Attract Chimpanzees Towards Known Food Patches in a Captive Setting
Authors: O’Bryan Lisa R. , Lambeth Susan P. , Schapiro Steven J. , Wilson Michael L. 
Published: November 2020

AbstractFood-associated calls have attracted much research attention due to their potential to refer to discovered food in a word-like manner. Nevertheless, their effect on receiver behavior remains unclear for many species. While some studies suggest that food-associated calls attract other foragers, other studies indicate that they repel others. We conducted playback studies to differentiate between these two hypotheses for the function of the chimpanzee (Pan troglodytes) food-associated ‘rough grunt’. We tested how acoustic playbacks of rough grunts (or control calls) from one of two known, identical food patches affected receivers’ foraging decisions in a captive setting. We found that participants were more likely than chance to first investigate the patch from which rough-grunts, but not control calls, were broadcast. However, neither condition increased the likelihood that participants fed first from a given patch. Our results support the hypothesis that rough-grunts attract receivers. However, since receivers were already aware of the presence of food, our results question whether rough-grunts attract by conveying information about discovered food, or rather, the signaler’s motivational state.
ISA API: An open platform for interoperable life science experimental metadata
Authors: Johnson David , Cochrane Keeva , Davey Robert P. , Etuk Anthony , Gonzalez-Beltran Alejandra , Haug Kenneth , Izzo Massimiliano , Larralde Martin , Lawson Thomas N. , Minotto Alice , Moreno Pablo , Nainala Venkata Chandrasekhar , O’Donovan Claire , Pireddu Luca , Roger Pierrick , Shaw Felix , Steinbeck Christoph , Weber Ralf J. M. , Sansone Susanna-Assunta , Rocca-Serra Philippe 
Published: November 2020

AbstractBackgroundThe Investigation/Study/Assay (ISA) Metadata Framework is an established and widely used set of open-source community specifications and software tools for enabling discovery, exchange and publication of metadata from experiments in the life sciences. The original ISA software suite provided a set of user-facing Java tools for creating and manipulating the information structured in ISA-Tab – a now widely used tabular format. To make the ISA framework more accessible to machines and enable programmatic manipulation of experiment metadata, a JSON serialization ISA-JSON was developed.ResultsIn this work, we present the ISA API, a Python library for the creation, editing, parsing, and validating of ISA-Tab and ISA-JSON formats by using a common data model engineered as Python object classes. We describe the ISA API feature set, early adopters and its growing user community.ConclusionsThe ISA API provides users with rich programmatic metadata handling functionality to support automation, a common interface and an interoperable medium between the two ISA formats, as well as with other life science data formats required for depositing data in public databases.
Patient-specific iPSCs carrying anSFTPCmutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease
Authors: Alysandratos Konstantinos-Dionysios , Russo Scott J. , Petcherski Anton , Taddeo Evan P. , Acín-Pérez Rebeca , Villacorta-Martin Carlos , Jean J. C. , Mulugeta Surafel , Blum Benjamin C. , Hekman Ryan M. , Vedaie Marall , Kook Seunghyi , Wambach Jennifer A. , Cole F. Sessions , Hamvas Aaron , Emili Andrew , Guttentag Susan H. , Shirihai Orian S. , Beers Michael F. , Kotton Darrell N. 
Published: November 2020

SummaryThe incompletely understood pathogenesis of pulmonary fibrosis (PF) and lack of reliable preclinical disease models have limited development of effective therapies. An emerging literature now implicates alveolar epithelial type 2 cell (AEC2) dysfunction as an initiating pathogenic event in the onset of a variety of PF syndromes, including adult idiopathic pulmonary fibrosis (IPF) and childhood interstitial lung disease (chILD). However, inability to access primary AEC2s from patients, particularly at early disease stages, has impeded identification of disease-initiating mechanisms. Here we present anin vitroreductionist model system that permits investigation of epithelial-intrinsic events that lead to AEC2 dysfunction over time using patient-derived cells that carry a disease-associated variant,SFTPCI73T, known to be expressed solely in AEC2s. After generating patient-specific induced pluripotent stem cells (iPSCs) and engineering their gene-edited (corrected) counterparts, we employ directed differentiation to produce pure populations of syngeneic corrected and mutant AEC2s, which we expand >1015foldin vitro, providing a renewable source of cells for modeling disease onset. We find that mutant iPSC-derived AEC2s (iAEC2s) accumulate large amounts of misprocessed pro-SFTPC protein which mistrafficks to the plasma membrane, similar to changes observedin vivoin the donor patient’s AEC2s. These changes result in marked reduction in AEC2 progenitor capacity and several downstream perturbations in AEC2 proteostatic and bioenergetic programs, including a late block in autophagic flux, accumulation of dysfunctional mitochondria with consequent time-dependent metabolic reprograming from oxidative phosphorylation to glycolysis, and activation of an NF-κB dependent inflammatory response. Treatment ofSFTPCI73Texpressing iAEC2s with hydroxychloroquine, a medication commonly prescribed to these patients, results in aggravation of autophagy perturbations and metabolic reprogramming. Thus, iAEC2s provide a patientspecific preclinical platform for modeling the intrinsic epithelial dysfunction associated with the inception of interstitial lung disease.
methylscaper: an R/Shiny app for joint visualization of DNA methylation and nucleosome occupancy in single-molecule and single-cell data
Authors: Knight Parker , Gauthier Marie-Pierre L. , Pardo Carolina E. , Darst Russell P. , Riva Alberto , Kladde Michael P. , Bacher Rhonda 
Published: November 2020

AbstractDifferential DNA methylation and chromatin accessibility are associated with disease development, particularly cancer. Methods that allow profiling of these epigenetic mechanisms in the same reaction and at the single-molecule or single-cell level continue to emerge. However, a challenge lies in jointly visualizing and analyzing the heterogeneous nature of the data and extracting regulatory insight. Here, we developed methylscaper, a visualization framework for simultaneous analysis of DNA methylation and chromatin landscapes. Methylscaper implements a weighted principle component analysis that orders sequencing reads, each providing a record of the chromatin state of one epiallele, and reveals patterns of nucleosome positioning, transcription factor occupancy, and DNA methylation. We demonstrate methylscaper’s utility on a long-read, single-molecule methyltransferase accessibility protocol for individual templates (MAPit) dataset and a single-cell nucleosome, methylation, and transcription sequencing (scNMT-seq) dataset. In comparison to other procedures, methylscaper is able to readily identify chromatin features that are biologically relevant to transcriptional status while scaling to larger datasets.Availability and implementationMethylscaper, is available on GitHub athttps://github.com/rhondabacher/methylscaper.Contactrbacher@ufl.edu
Prediction of Covid-19 Infections Through December 2020 for 10 US States Incorporating Outdoor Temperature and School Re-Opening Effects-October Update
Authors: Newell Ty 
Published: November 2020

AbstractControl of SARS-CoV-2 transmission requires control of two human behaviors. A two-parameter, human behavior Covid-19 infection growth model continues to accurately predict total infections based on gross human interaction and local human interaction behaviors for 10 US States (NY, WA, GA, IL, MN, FL, OH, MI, CA, NC). Since prediction model initiation on July 27, 2020, total infections for 8 states have grown by more than 200%. Only New York (23% infection growth) and Florida (189% infection growth) have grown less.October displays combined impacts of increased social interactions as schools and businesses increase physical gatherings, coupled with climate dependent local interactions. The US, on average as of the end of October, has an Infection Parameter (IP) of 3.4 representing accelerating infection growth. Gross human interactions must be reduced by 15% or local interaction behavior (eg, face mask usage, ventilation) must be improved to reduce disease transmission efficiency by 27% in order to reach the linear infection growth boundary separating accelerating infection growth from decaying infection growth regions.Eastern States (NY and NC) have had mild fall temperatures, which increases outdoor activities and increases building fresh air ventilation rates that suppress virus transmission efficiency. Mild temperatures in southern States (GA, FL and CA) during October have also helped suppress virus transmission. Midwest States experienced highly elevated infection rates due to combined effects of school openings coupled with a truncated fall season. WA stayed in the beneficial 70F (22C) to 50F (10C) zone through October, with minimal accelerated infection growth, but is now entering its heating season with average outdoor temperatures below 50F that are contributing to increased disease transmission efficiency.
Structural Investigation of Oat Protein Isolate in Aqueous Medium by using Synchrotron Small-angle X-ray Scattering
Authors: Li Ji , Huang Qingrong 
Published: November 2020

AbstractOat protein isolate (OPI) is among the plant proteins with valuable functionalities (e.g. emulsification) during daily supplement intake. Understanding their structures helps to manipulate oat proteins at small scale, which enables the appropriate deployment of their functions. Based upon such understanding, the molecular structure of oat protein isolate (OPI) in aqueous medium was investigated by synchrotron small-angle X-ray scattering (SAXS), and this study allows a structural reconstitution of OPI in aqueous medium. Besides, this SAXS study is complimentary to the previous study (Liu et al.J. Agric. Food Chem. 2009, 57, 4552–4558)1. From form factor fitting, we confirmed that OPI aqueous solutions at low concentrations (0.3~2 mg/mL) obtained a disk conformation (41.4×41.4×10.2 Å3). Once protein concentration increased to 5 mg/mL and 10 mg/mL, the individual disk proteins formed large-dimensional rodlike aggregates, which was evidenced by the analyses of effective structure factor and pair distribution function (PDF). Based on the PDF results, theab initiomodels of OPI particles at low concentrations (0.3 mg/mL to 2.0 mg/mL) were restored by using GASBOR algorithm. Finally, we found that weak attraction between OPI particles occurred, which was verified by second virial coefficient and pair potential.