bluuebunny/crossref_metadata_2025_split huggingface dataset:
A macromutation eliminates colour patterning in captive butterflies
Authors: Hanly Joseph J. , Livraghi Luca , Heryanto Christa , McMillan W. Owen , Jiggins Chris D. , Gilbert Lawrence E. , Martin Arnaud 
Published: November 2021

AbstractCaptive populations often harbor variation that is not present in the wild due to artificial selection. Recent efforts to map this variation have provided insights into the genetic and molecular basis of variation. Heliconius butterflies display a large array of pattern variants in the wild and the genetic basis of these patterns has been well-described. Here we sought to identify the genetic basis of an unusual pattern variant that is instead found in captivity, the ivory mutant, in which all scales on both the wings and body become white or yellow. Using a combination of autozygosity mapping and coverage analysis from 37 captive individuals, we identify a 78kb deletion at the cortex wing patterning locus as the ivory mutation. This deletion is undetected among 458 wild Heliconius genomes samples, and its dosage explains both homozygous and heterozygous ivory phenotypes found in captivity. The deletion spans a large 5’ region of the cortex gene that includes a facultative 5’UTR exon detected in larval wing disk transcriptomes. CRISPR mutagenesis of this exon replicates the wing phenotypes from coding knock-outs of cortex, consistent with a functional role of ivory-deleted elements in establishing scale color fate. Population demographics reveal that the stock giving rise to the ivory mutant has a mixed origin from across the wild range of H. melpomene, and supports a scenario where the ivory mutation occurred after the introduction of cortex haplotypes from Ecuador. Homozygotes for the ivory deletion are inviable, joining 40 other examples of allelic variants that provide heterozygous advantage in animal populations under artificial selection by fanciers and breeders. Finally, our results highlight the promise of autozygosity and association mapping for identifying the genetic basis of aberrant mutations in captive insect populations.
Particle interactions and their effect on magnetic particle imaging and spectroscopy
Authors: Moor Lorena , Scheibler Subas , Gerken Lukas , Scheffler Konrad , Thieben Florian , Knopp Tobias , Herrmann Inge K. , Starsich Fabian H. L. 
Published: November 2021

AbstractTracer and thus signal stability is crucial for an accurate diagnosis via magnetic particle imaging (MPI). However, MPI-tracer nanoparticles frequently agglomerate during their in vivo applications leading to particle interactions. Here, we investigate the influence of such magnetic coupling phenomena on the MPI signal. We prepared and characterized Zn0.4Fe2.6O4 nanoparticles and controlled their interparticle distance by variying SiO2 coating thickness. The silica shell affected the magnetic properties indicating stronger particle interactions for a smaller interparticle distance. The SiO2-coated Zn0.4Fe2.6O4 outperformed the bare sample in magnetic particle spectroscopy (MPS) in terms of signal/noise, however, the shell thickness itself only weakly influenced the MPS signal. To investigate the importance of magnetic coupling effects in more detail, we benchmarked the MPS signal of the bare and SiO2-coated Zn-ferrites against commercially available PVP-coated Fe3O4 nanoparticles in water and PBS. PBS is known to destabilize nanoparticles mimicking an agglomeration in vivo. The bare and coated Zn-ferrites showed excellent signal stability, despite their agglomeration in PBS. We attribute this to their aggregated morphology formed during their flame-synthesis. On the other hand, the MPS signal of commercial PVP-coated Fe3O4 strongly decreased in PBS compared to water, indicating strongly changed particle interactions. The relevance of this effect was further investigated in a mammalian cell model. For PVP-coated Fe3O4, we could detect a strong discrepancy between the particle concentration obtained from the MPS signal and the actual concentration determined via ICP-MS. The same trend was observed during their MPI analysis; while SiO2-coated Zn-ferrites could be precisely located in water and PBS, PVP-coated Fe3O4 could not be detected in PBS at all. This drastically limits the sensitivity and also general applicability of MPI using such standard commercial tracers and highlights the advantages of our flame-made Zn-ferrites concerning signal stability and ultimately diagnostic accuracy.
Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike
Authors: Díaz-Salinas Marco A. , Li Qi , Ejemel Monir , Yurkovetskiy Leonid , Luban Jeremy , Shen Kuang , Wang Yang , Munro James B. 
Published: November 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Förster resonance energy transfer (smFRET) imaging we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and the B.1 variant (D614G). We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails.
Joint modeling of choices and reaction times based on Bayesian contextual behavioral control
Authors: Schwöbel Sarah , Markovic Dimitrije , Smolka Michael N. , Kiebel Stefan 
Published: November 2021

AbstractIn cognitive neuroscience and psychology, reaction times are an important behavioral measure. However, in instrumental learning and goal-directed decision making experiments, findings often rely only on choice probabilities from a value-based model, instead of reaction times. Recent advancements have shown that it is possible to connect value-based decision models with reaction time models. However, typically these models do not provide an integrated account of both value-based choices and reaction times, but simply link two types of models. Here, we propose a novel integrative joint model of both choices and reaction times by combining a mechanistic account of Bayesian sequential decision making with a sampling procedure. This allows us to describe how internal uncertainty in the planning process shapes reaction time distributions. Specifically, we use a recent context-specific Bayesian forward planning model which we extend by a Markov chain Monte Carlo (MCMC) sampler to obtain both choices and reaction times. As we will show this makes the sampler an integral part of the decision making process and enables us to reproduce, using simulations, well-known experimental findings in value based-decision making as well as classical inhibition and switching tasks. Specifically, we use the proposed model to explain both choice behavior and reaction times in instrumental learning and automatized behavior, in the Eriksen flanker task and in task switching. These findings show that the proposed joint behavioral model may describe common underlying processes in these different decision making paradigms.Author summaryMany influential results in psychology and cognitive neuroscience rest on reaction time effects in behavioral experiments, for example in studies about human decision making. For decisions that rest on planning, findings often rely on analyses using specific computational models. Until recently, these models did not allow for analysis of reaction times. In this article we introduce a new model of how to explain both choices and reaction times in decision making experiments that involve planning. Importantly, the model explains how the brain can make good decisions quickly, even in the face of many potential choices and in complex environments.
Selective Control of Synaptically-Connected Circuit Elements by All-Optical Synapses
Authors: Prakash Mansi , Murphy Jeremy , St Laurent Robyn , Friedman Nina , Crespo Emmanuel L. , Bjorefeldt Andreas , Pal Akash , Bhagat Yuvraj , Kauer Julie A. , Shaner Nathan C. , Lipscombe Diane , Moore Christopher I. , Hochgeschwender Ute 
Published: November 2021

AbstractUnderstanding percepts, engrams and actions requires methods for selectively modulating synaptic communication between specific subsets of interconnected cells. Here, we develop an approach to control synaptically connected elements using bioluminescent light: Luciferase-generated light, originating from a presynaptic axon terminal, modulates an opsin in its postsynaptic target. Vesicular-localized luciferase is released into the synaptic cleft in response to presynaptic activity, creating a real-time ‘Optical Synapse’. Light production is under experimenter-control by introduction of the small molecule luciferin. Signal transmission across this optical synapse is temporally defined by the presence of both the luciferin and presynaptic activity. We validate synaptic ‘Interluminescence’ by multi-electrode recording in cultured neurons and in mice in vivo. Interluminescence represents a powerful approach to achieve synapse-specific and activity-dependent circuit control during behavior in vivo.
Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients
Authors: Adamik Barbara , Ambrożek-Latecka Magdalena , Dragan Barbara , Jeznach Aldona , Śmiechowicz Jakub , Goździk Waldemar , Skirecki Tomasz 
Published: November 2021

AbstractPurposeDevelopment of targeted biological therapies for COVID-19 requires reliable biomarkers that could help indicate the responding patients. Hyperactivation of the inflammasome by SARS-CoV2 virus is hypothesized to contribute to severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins at the admission to the intensive care unit (ICU).Patients and methodsPlasma samples were obtained from 45 critically ill COVID-19 patients and from 10 patients any without any signs of infection (TBI, traumatic brain injury) on admission to the ICU. The concentration of IL-1α, IL-1β, IL-18, IL-1RA, galectin-1, ASC, LDH, ferritin, and gasdermin D were analyzed. A novel cell-free caspase-1 plasma assay was developed by inhibitor-based immunoprecipitation followed by Western Blot. Demographic and clinical characteristics were recorded.ResultsIn-hospital mortality in COVID-19 patients reached 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 vs. 30764.20 pg/ml, p=0.007), but other inflammasome-related biomarkers were at similar concentrations. Patients with SOFA score of >9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison to low-risk patients (25551.3 pg/ml vs 16302.7 pg/ml, p=0.014; 14.5 pg/ml vs 39.4 pg/ml, p=0.04, respectively). Statistically significant correlations were observed between: IL-1α and platelets (r=-0.37), IL-1β and platelets (r=-0.36), ferritin and INR (r=0.39). Activated caspase-1 p35 was detectable in 12/22 COVID-19 patients but in none of the TBI patients. Its presence was related with higher fibrinogen and lower D-dimers. Moreover, the densitometric analysis showed a significantly higher amount of p35 in patients with SOFA> 9.ConclusionOur results indicate that the systemic markers of activation of the inflammasome in critically ill COVID-19 patients is not directly related with outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.
Pay-it-forward to improve influenza vaccine uptake and public engagement among children and older adults in China: A quasi-experimental pragmatic trial
Authors: Wu Dan , Jin Chenqi , Bessame Khaoula , Tang Fanny Fong-Yi , Ong Jason J. , Wang Zaisheng , Xie Yewei , Jit Mark , Larson Heidi J. , Chantler Tracey , Lin Leesa , Gong Wenfeng , Yang Fan , Jing Fengshi , Wei Shufang , Cheng Weibin , Zhou Yi , Ren Nina , Qiu Shuhao , Bao Jianmin , Wen Liufen , Yang Qinlu , Tian Junzhang , Tang Weiming , Tucker Joseph D. 
Published: November 2021

ABSTRACTBackgroundChina has low seasonal influenza vaccination rates among children and older adults. This quasi-experimental pragmatic trial examined the effectiveness of a pay-it-forward intervention on influenza vaccination compared to standard-of-care (user-paid vaccination) among children and older people in China. Pay-it-forward offered a free influenza vaccine from a local group and an opportunity to donate financially to support future individuals.MethodsAt each of the three study sites, participants were recruited into the standard-of-care arm first until expected sample size was reached and then recruited into the pay-it-forward arm. The primary outcome was vaccine uptake. Secondary outcomes included vaccine confidence and costs. Regression methods compared influenza vaccine uptake and vaccine confidence between the two arms.ResultsAmong 300 participants enrolled, 55/150(36.7%) in the standard-of-care arm 111/150(74.0%) in the pay-it-forward arm received an influenza vaccine. People in the pay-it-forward arm were more likely to receive the vaccine compared to people in the standard-of-care arm (adjusted odds ratio (aOR)= 6.7, 95%CI [2.7, 16.6] among children; aOR=5.0, [2.3, 10.8] among older adults). People in the pay-it-forward arm had greater confidence in vaccine safety, importance, and effectiveness. In the pay-it-forward arm, 107/111 (96.4%) of participants donated money for subsequent vaccinations, and 19 of 60 invited (31.7%) created postcard messages. The pay-it-forward arm had a lower economic cost per person vaccinated ($45.60) than the standard-of-care arm ($64.67).ConclusionsPay-it-forward was effective in improving influenza vaccine uptake and public engagement. Our data have implications for pro-social interventions to enhance influenza vaccine uptake in countries where influenza vaccines are available for a fee.Trial registrationChiCTR2000040048Main point summaryPay-it-forward substantially increased influenza vaccine uptake among children and older adults compared to standard of care user-paid vaccination.
Gigavalent display of proteins on monodisperse polyacrylamide hydrogels as a versatile modular platform for functional assays and protein engineering
Authors: Fryer Thomas , Rogers Joel David , Mellor Christopher , Minter Ralph , Hollfelder Florian 
Published: November 2021

AbstractThe robust modularity of biological components that are assembled into complex functional systems is central to synthetic biology. Here we apply modular “plug and play” design principles to a microscale solid phase protein display system that enables protein purification and functional assays for biotherapeutics. Specifically, we capture protein molecules from cell lysates on polyacrylamide hydrogel display beads (‘PHD beads’), made in microfluidic droplet generators. These monodisperse PHD beads are decorated with predefined amounts of anchors, methacrylate-PEG-benzylguanine (BG) and methacrylate-PEG-chloroalkane (CA). Anchors form covalent bonds with fusion proteins bearing cognate tag recognition (SNAP and Halo-tags) in specific, orthogonal and stable fashion. Given that these anchors are copolymerised throughout the 3D structure of the beads, proteins are also distributed across the entire bead sphere, allowing attachment of ∼109 protein molecules per bead (Ø 20 μm). This mode of attachment reaches a higher density than possible on widely used surface-modified beads, and additionally mitigates surface effects that often complicate studies with proteins on beads. We showcase a diverse array of protein modules that enable the secondary capture of proteins, either non-covalently (IgG and SUMO-tag) or covalently (SpyCatcher, SpyTag, SnpCatcher and SnpTag). Proteins can be displayed in their monomeric forms, but also reformatted as a multivalent display (using secondary capture modules that create branches) to test the contributions of avidity and multivalency towards protein function. Finally, controlled release of modules by irradiation of light is achieved by incorporating the photocleavable protein PhoCl: irradiation severs the displayed protein from the solid support, so that functional assays can be carried out in solution. As a demonstration of the utility of valency engineering, an antibody drug screen is performed, in which an anti-TRAIL-R1 scFv protein is released into solution as monomers-hexamers, showing a ∼50-fold enhanced potency in the pentavalent format. The ease of protein purification on solid support, quantitative control over presentation and release of proteins and choice of valency make this experimental format a versatile, modular platform for large scale functional analysis of proteins, in bioassays of protein-protein interactions, enzymatic catalysis and bacteriolysis.Table of Contents Graphics
Plasma donation induces a protein expression profile shift in circulating human blood
Authors: Flickenger Rob 
Published: November 2021

AbstractCommercial plasma donation yields a change in protein concentration similar to that observed in therapeutic plasma exchange (TPE) in humans. The post-donation expression profile shows an increase in many proteins after even a single donation, and the effect is enhanced with additional donations. Unlike TPE, human plasma donation returns saline without albumin to the donor, thus eliminating supplemental albumin as a contributing factor. The observed fold change falls outside the variation expected by natural circadian expression changes.N=6 humans (four donors, one monthly control and one circadian test). Seventeen antibody tests were performed, measuring the concentration of 507 proteins for each test.
Study Protocol of A Phase II Study to Evaluate Safety and Efficacy of Neo-adjuvant Pembrolizumab and Radiotherapy in Localized Rectal Cancer
Authors: Corrò Claudia , Buchs Nicolas C. , Tihy Matthieu , Durham-Faivre André , Bichard Philippe , Frossard Jean-Louis , Puppa Giacomo , McKee Thomas , Roth Arnaud , Zilli Thomas , Trembleau Christelle , Marco Mariagrazia Di , Dutoit Valérie , Dietrich Pierre-Yves , Ris Frédéric , Kössler Thibaud 
Published: November 2021

AbstractBackgroundReshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve the treatment of cancers. Nevertheless, responsiveness to these treatments is often correlated with the extent of the T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor infiltration and, therefore, do not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy may have profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immunotherapy was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immunotherapy have never been tested in these tumors.MethodsOur clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized microsatellite stable rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5Gy x 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed after three weeks from the last pembrolizumab injection. Our clinical trial also includes an extensive research program involving the transcriptomic and proteomic analysis of blood and tumor samples throughout the course of the treatment.DiscussionOur study is the first clinical trial to provide with safety and efficacy information of this novel treatment approach in rectal cancer, leading to a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer better insight into immunological changes within the tumor and blood during treatment. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients.Trial registrationThis study was registered with www.clinicaltrial.gov: NCT04109755. Registration date: June, 2020.
Polyamines mediate enterovirus attachment directly and indirectly through cellular heparan sulfate synthesis
Authors: Hulsebosch Bridget M. , Omoba Oreoluwa S. , LoMascolo Natalie J. , Mounce Bryan C. 
Published: November 2021

AbstractProductive viral infection begins with attachment to a susceptible cell, and viruses have evolved complex mechanisms to attach to and subsequently enter cells. Prior to engagement with a cellular receptor, viruses frequently interact with nonspecific attachment factors that can facilitate virus-receptor interactions and viral entry. Polyamines, small positively-charged molecules abundant in mammalian cells, mediate viral attachment, though the mechanism was not fully understood. Using the Coxsackievirus B3 (CVB3) enterovirus model system, we show that polyamines mediate viral attachment both directly and indirectly. The polyamine putrescine specifically enhances viral attachment to cells depleted of polyamines. Putrescine’s positive charge mediates its ability to enhance viral attachment, and polyamine analogs are less efficient at mediating viral attachment. In addition to this direct role of polyamines in attachment, polyamines facilitate the cellular expression of heparan sulfates, negatively-charged molecules found on the cell surface. In polyamine-depleted cells, heparan sulfates are depleted from the surface of cells, resulting in reduced viral attachment. We find that this is due to polyamines’ role in the process of hypusination of eukaryotic initiation factor 5A, which facilitates cellular translation. These data highlight the important role of polyamines in mediating cellular attachment, as well as their function in facilitating cellular heparan sulfate synthesis.
Synthetic periphyton as a model system to understand species dynamics in complex microbial freshwater communities
Authors: Lamprecht Olga , Wagner Bettina , Derlon Nicolas , Tlili Ahmed 
Published: November 2021

AbstractPhototrophic biofilms, also known as periphyton, are microbial freshwater communities that drive crucial ecological processes in streams and lakes. Gaining a deep mechanistic understanding of the biological processes occurring in natural periphyton remains challenging due to the high complexity and variability of such communities. To address this challenge, we rationally developed a workflow to construct a synthetic community by co-culturing 26 phototrophic species (i.e., diatoms, green algae and cyanobacteria) that were inoculated in a successional sequence to create a periphytic biofilm on glass slides. We show that this community is diverse, stable and highly reproducible in terms of microbial composition, function and 3D spatial structure of the biofilm. We also demonstrate the ability to monitor microbial dynamics at the single species level during periphyton development and how their abundances are impacted by stressors such as increased temperature and a herbicide, singly and in combination. Overall, such a synthetic periphyton, grown under controlled conditions, can be used as a model system for theory testing through targeted manipulation.