bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scale-free dynamics in animal groups and brain networks
Authors: Ribeiro Tiago L. , Chialvo Dante R. , Plenz Dietmar 
Published: December 2020

AbstractCollective phenomena fascinate by the emergence of order in systems composed of a myriad of small entities. They are ubiquitous in nature and can be found over a vast range of scales in physical and biological systems. Their key feature is the seemingly effortless emergence of adaptive collective behavior that cannot be trivially explained by the properties of the system’s individual components. This perspective focuses on recent insights into the similarities of correlations for two apparently disparate phenomena: flocking in animal groups and neuronal ensemble activity in the brain. We first will summarize findings on the spontaneous organization in bird flocks and macro-scale human brain activity utilizing correlation functions and insights from critical dynamics. We then will discuss recent experimental findings that apply these approaches to the collective response of neurons to visual and motor processing, i.e. to local perturbations of neuronal networks at the meso- and microscale. We show how scale-free correlation functions capture the collective organization of neuronal avalanches in evoked neuronal populations in nonhuman primates and between neurons during visual processing in rodents. These experimental findings suggest that the coherent collective neural activity observed at scales much larger than the length of the direct neuronal interactions is demonstrative of a phase transition. We discuss the experimental support for either discontinuous or continuous phase transitions. We conclude that at or near a phase-transition neuronal information can propagate in the brain with the same efficiency as proposed to occur in the collective adaptive response observed in some animal groups.
Molecular pathways to high-level azithromycin resistance inNeisseria gonorrhoeae
Authors: Laumen J.G.E. , Manoharan-Basil S.S. , Verhoeven E , Abdellati S , De Baetselier I , Crucitti T , Xavier B.B. , Chapelle S , Lammens C , Van Dijck C , Malhotra-Kumar S , Kenyon C 
Published: December 2020

AbstractObjectivesThe prevalence of azithromycin resistance inNeisseria gonorrhoeaeis increasing in numerous populations worldwide. The aim of this study was to characterize the genetic pathways leading to high-level azithromycin resistance.MethodsA customized morbidostat was used to subject twoN. gonorrhoeaereference strains (WHO-F and WHO-X) to dynamically sustained azithromycin pressure. We tracked stepwise evolution of resistance by whole genome sequencing.ResultsWithin 26 days, all cultures evolved high-level azithromycin resistance. Typically, the first step towards resistance was found in transitory mutations in genesrplD,rplVandrpmH(encoding the ribosomal proteins L4, L22 and L34 respectively), followed by mutations in the MtrCDE-encoded efflux pump and the 23S rRNA gene. Low-to high-level resistance was associated with mutations in the ribosomal proteins and MtrCDE-encoded efflux pump. However, high-level resistance was consistently associated with mutations in the 23S ribosomal RNA - mainly the well-known A2059G and C2611T mutations, but also at position A2058G.ConclusionsThis study enabled us to track previously reported mutations and identify novel mutations in ribosomal proteins (L4, L22 and L34) that may play a role in the genesis of azithromycin resistance inN. gonorrhoeae.
Mouse and Human Antibodies that Bind HLA-E-Leader Peptide Complexes and Enhance NK Cell Cytotoxicity
Authors: Li Dapeng , Brackenridge Simon , Walters Lucy C. , Swanson Olivia , Harlos Karl , Rozbesky Daniel , Cain Derek W. , Wiehe Kevin , Scearce Richard M. , Barr Maggie , Mu Zekun , Parks Robert , Quastel Max , Edwards Robert J. , Wang Yunfei , Rountree Wes , Saunders Kevin O. , Ferrari Guido , Borrow Persephone , Yvonne Jones E. , Munir Alam S. , Azoitei Mihai L. , Gillespie Geraldine M. , McMichael Andrew J. , Haynes Barton F. 
Published: December 2020

ABSTRACTHLA-E is a non-classical class Ib molecule that has limited polymorphism and binds HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we isolated a murine IgM antibody 3H4, that specifically recognized HLA-E-VL9 bound complexes and enhanced killing of HLA-E-VL9-expressing cells by an NKG2A+NK cell line. Structural analysis revealed how 3H4 prevents CD94/NKG2A docking on HLA-E-VL9 by binding with an overlapping footprint. Uponin vitromaturation, an affinity-optimized 3H4 IgG showed enhanced NK killing of HLA-E-VL9-expressing cells. Remarkably, HLA-E-VL9-specific IgM autoantibodies with similar specificity and functions to 3H4 were subsequently isolated from naïve B cells of cytomegalovirus (CMV)-negative, healthy male human donors. Thus, a repertoire of germline low affinity HLA-E-VL9-reactive antibodies are present in both naïve human and murine B cell repertoires. These antibodies can enhance NK cell cytotoxicity and therefore have potential for therapeutic modulation of NK cell function.
Early or late gestational exposure to maternal immune activation alters neurodevelopmental trajectories in mice: an integrated neuroimaging, behavioural, and transcriptional study
Authors: Guma Elisa , Bordignon Pedro , Devenyi Gabriel A. , Gallino Daniel , Anastassiadis Chloe , Cvetkovska Vedrana , Barry Amadou , Snook Emily , Germann Jurgen , Greenwood Celia M.T. , Misic Bratislav , Bagot Rosemary C. , Chakravarty M. Mallar 
Published: December 2020

AbstractPrenatal maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders. How gestational timing of MIA-exposure differentially impacts downstream development remains unclear. Here, we characterize neurodevelopmental trajectories of mice exposed to MIA induced by poly I:C either early (gestational day [GD]9) or late (GD17) in gestation using longitudinal structural magnetic resonance imaging from weaning to adulthood. Early MIA-exposure associated with accelerated brain volume increases in adolescence/early-adulthood that normalized in later adulthood, in regions including the striatum, hippocampus, and cingulate cortex. Similarly, alterations in anxiety, stereotypic, and sensorimotor gating behaviours observed in adolescence normalized in adulthood. In contrast, MIA-exposure in late gestation had less impact on anatomical and behavioural profiles. Using a multivariate technique to relate imaging and behavioural variables for the time of greatest alteration, i.e. adolescence/early adulthood, we demonstrate that variation in anxiety, social, and sensorimotor gating associates significantly with volume of regions including the dorsal and ventral hippocampus, and anterior cingulate cortex. Using RNA sequencing to explore the molecular underpinnings of region-specific alterations in early MIA-exposed mice in adolescence, we observed the most transcriptional changes in the dorsal hippocampus, with regulated genes enriched for fibroblast growth factor regulation, autistic behaviours, inflammatory pathways, and microRNA regulation. This indicates that MIA in early gestation perturbs brain development mechanisms implicated in neurodevelopmental disorders. Our findings demonstrate the inherent strength of an integrated hypothesis- and data-driven approach in linking brain-behavioural alterations to the transcriptome to understand how MIA confers risk for major mental illness.
Hebbian plasticity in parallel synaptic pathways: A circuit mechanism for systems memory consolidation
Authors: Remme Michiel , Bergmann Urs , Alevi Denis , Schreiber Susanne , Sprekeler Henning , Kempter Richard 
Published: December 2020

AbstractSystems memory consolidation involves the transfer of memories across brain regions and the transformation of memory content. For example, declarative memories that transiently depend on the hippocampal formation are transformed into long-term memory traces in neocortical networks, and procedural memories are transformed within cortico-striatal networks. These consolidation processes are thought to rely on replay and repetition of recently acquired memories, but the cellular and network mechanisms that mediate the changes of memories are poorly understood. Here, we suggest that systems memory consolidation could arise from Hebbian plasticity in networks with parallel synaptic pathways — two ubiquitous features of neural circuits in the brain. We explore this hypothesis in the context of hippocampus-dependent memories. Using computational models and mathematical analyses, we illustrate how memories are transferred across circuits and discuss why their representations could change. The analyses suggest that Hebbian plasticity mediates consolidation by transferring a linear approximation of a previously acquired memory into a parallel pathway. Our modelling results are further in quantitative agreement with lesion studies in rodents. Moreover, a hierarchical iteration of the mechanism yields power-law forgetting — as observed in psychophysical studies in humans. The predicted circuit mechanism thus bridges spatial scales from single cells to cortical areas and time scales from milliseconds to years.Author summaryAfter new memories are acquired, they can be transferred over time into other brain areas — a process called systems memory consolidation. For example, new declarative memories, which refer to the conscious memory of facts and events, depend on the hippocampus. Older declarative memories, however, also rely on neocortical networks. The cellular mechanisms underlying such a transfer are poorly understood. In this work, we show that a simple and in the brain ubiquitous connectivity pattern, combined with a standard learning rule, leads to gradual memory transfer. We illustrate our proposed mechanism in numerical simulations and mathematical analyses. At the neurophysiological level, our theory explains experimental findings on memory storage in the hippocampal formation when specific pathways between neural populations are disrupted. At the psychophysical level, we can account for the power-law forgetting curves typically found in humans. A consequence of the proposed model is that consolidated memories can yield faster responses because they are stored in increasingly shorter synaptic pathways between sensory and motor areas. By giving a mechanistic explanation of the consolidation process, we contribute to the understanding of the transfer of memories and the reorganization of memories over time.
Using a non-destructive sugar-feeding assay for sporozoite detection and estimating the extrinsic incubation period ofPlasmodium falciparumin mosquito vectors
Authors: Guissou Edwige , Waite Jessica L. , Jones Matthew , Bell Andrew S. , Suh Eunho , Yameogo Koudraogo B. , Djegbe Nicaise , Da Dari F. , Hien Domonbabele FdS , Yerbanga Rakiswende S. , Ouedraogo Anicet G. , Dabiré Kounbobr R. , Cohuet Anna , Thomas Matthew B. , Lefèvre Thierry 
Published: December 2020

AbstractDespite its epidemiological importance, the timePlasmodiumparasites take to achieve development in the vector mosquito (the extrinsic incubation period, EIP) remains poorly characterized. A novel non-destructive assay designed to estimate EIP in single mosquitoes, and more broadly to studyPlasmodium–Anophelesvectors interactions, is presented. The assay uses small pieces of cotton wool soaked in sugar solution to collect malaria sporozoites from individual mosquitoes during sugar feeding to monitor infection status over time. This technique has been tested across four natural malaria mosquito species of Africa and Asia, six parasite isolates ofPlasmodium falciparum, and across a range of temperatures relevant to malaria transmission in field conditions. We find that monitoring individual infectious mosquitoes is feasible, although due to the frequency of mosquito sugar feeding and inter-individual variation in infection intensity, there is inherent risk that this technique will result in some false negatives. The sensitivity rate ranged from 0.27 to 0.81 depending on mosquito species and on infection intensity in mosquitoes used to collect saliva. Using this non-destructive technique, the estimated median extrinsic incubation period ofP. falciparumat 27°C was 11 to 14 days depending on mosquito species and parasite isolate. Long-term individual tracking also revealed that sporozoite transfer onto cotton wool can occur at least until day 40 post-infection. In addition to contributing to a better understanding of EIP and mosquito to human transmission with implications for improving epidemiological models, this technique also allows to link different transmission traits at the mosquito individual level. As one example, we found a significant relationship between EIP and mosquito lifespan, with short individual EIP associated with short mosquito lifespan. Correlations between mosquito/parasite traits often reveal trade-offs and constraints and have important implications for understanding the evolution of parasite transmission strategies.
An Omic and Multidimensional Spatial Atlas from Serial Biopsies of an Evolving Metastatic Breast Cancer
Authors: Johnson Brett E. , Creason Allison L. , Stommel Jayne M. , Keck Jamie M. , Parmar Swapnil , Betts Courtney B. , Blucher Aurora , Boniface Christopher , Bucher Elmar , Burlingame Erik , Camp Todd , Chin Koei , Eng Jennifer , Estabrook Joseph , Feiler Heidi S. , Hu Zhi , Kolodzie Annette , Kong Ben L. , Labrie Marilyne , Lee Jinho , Leyshock Patrick , Mitri Souraya , Patterson Janice , Riesterer Jessica L. , Sivagnanam Shamilene , Somers Julia , Sudar Damir , Thibault Guillaume , Zheng Christina , Nan Xiaolin , Heiser Laura M. , Spellman Paul T. , Thomas George , Demir Emek , Chang Young Hwan , Coussens Lisa M. , Guimaraes Alexander R. , Corless Christopher , Goecks Jeremy , Bergan Raymond , Mitri Zahi , Mills Gordon B. , Gray Joe W. 
Published: December 2020

SummaryMechanisms of therapeutic resistance manifest in metastatic cancers as tumor cell intrinsic alterations and extrinsic microenvironmental influences that can change during treatment. To support the development of methods for the identification of these mechanisms in individual patients, we present here an Omic and Multidimensional Spatial (OMS) Atlas generated from four serial biopsies of a metastatic breast cancer patient during 3.5 years of therapy. This resource links detailed, longitudinal clinical metadata including treatment times and doses, anatomic imaging, and blood-based response measurements to exploratory analytics including comprehensive DNA, RNA, and protein profiles, images of multiplexed immunostaining, and 2- and 3-dimensional scanning electron micrographs. These data reveal aspects of therapy-associated heterogeneity and evolution of the cancer’s genome, signaling pathways, immune microenvironment, cellular composition and organization, and ultrastructure. We present illustrative examples showing how integrative analyses of these data provide insights into potential mechanisms of response and resistance, and suggest novel therapeutic vulnerabilities.
Single Cell Sequencing Reveals Glial Specific Responses to Tissue Processing & Enzymatic Dissociation in Mice and Humans
Authors: Marsh Samuel E. , Kamath Tushar , Walker Alec J. , Dissing-Olesen Lasse , Hammond Timothy R. , Young Adam M.H. , Abdulraouf Abdulraouf , Nadaf Naeem , Dufort Connor , Murphy Sarah , Kozareva Velina , Vanderburg Charles , Hong Soyon , Bulstrode Harry , Hutchinson Peter J. , Gaffney Daniel J. , Franklin Robin J.M. , Macosko Evan Z. , Stevens Beth 
Published: December 2020

AbstractA key aspect of nearly all single cell experiments is the necessity to dissociate intact tissues into single cell suspensions for processing. While many protocols have been optimized for optimal cell yield, they have often overlooked the effects that dissociation can have onex vivogene expression changes during this process. Microglia, the brain’s resident macrophages, are a highly dynamic population that are extremely sensitive to their microenvironment and have been shown to dramatically alter their transcriptome upon stimulation. We demonstrate that use of enzymatic dissociation methods on mouse central nervous system (CNS) tissue induces an aberrant gene expression signature in microglia that can significantly confound downstream analysis. To minimize this issue, we developed a flexible protocol, that can be used with existing enzymatic protocols for fresh tissue, to eliminate artifactual gene expression while allowing for increased cell type diversity and yield. We demonstrate efficacy of this protocol in analysis of diverse CNS cell types and sorted myeloid populations while using enzymatic dissociation. Generation of new and reanalysis of previously published human brain single nucleus RNAseq (snRNA-seq) datasets reveal that a similar signature is also present in post-mortem tissue. Through novel snRNA-seq analysis of acutely-resected neurosurgical tissue we demonstrate that this signature can be induced in human tissue due to technical differences in sample processing. These results provide key insight into the potential confounds of enzymatic digestion and provide a solution to allow for enzymatic digestion for scRNA-seq while avoidingex vivotranscriptional artifacts. Analysis of human tissue reveals potential for artifacts in current and future snRNA-seq datasets that will require deeper analysis and careful consideration to separate true biology from artifacts related to post-mortem processes.
MASiVar: Multisite, Multiscanner, and Multisubject Acquisitions for Studying Variability in Diffusion Weighted Magnetic Resonance Imaging
Authors: Cai Leon Y. , Yang Qi , Kanakaraj Praitayini , Nath Vishwesh , Newton Allen T. , Edmonson Heidi A. , Luci Jeffrey , Conrad Benjamin N. , Price Gavin R. , Hansen Colin B. , Kerley Cailey I. , Ramadass Karthik , Yeh Fang-Cheng , Kang Hakmook , Garyfallidis Eleftherios , Descoteaux Maxime , Rheault Francois , Schilling Kurt G. , Landman Bennett A. 
Published: December 2020

ABSTRACTPurposeDiffusion weighted imaging (DWI) allows investigators to identify structural, microstructural, and connectivitybased differences between subjects, but variability due to session and scanner biases is a challenge.MethodsTo investigate DWI variability, we present MASiVar, a multisite dataset consisting of 319 diffusion scans acquired at 3T from b = 1000 to 3000 s/mm2 across 14 healthy adults, 83 healthy children (5 to 8 years), three sites, and four scanners as a publicly available, preprocessed, and de-identified dataset. With the adult data, we demonstrate the capacity of MASiVar to simultaneously quantify the intrasession, intersession, interscanner, and intersubject variability of four common DWI processing approaches: (1) a tensor signal representation, (2) a multi-compartment neurite orientation dispersion and density model, (3) white matter bundle segmentation, and (4) structural connectomics. Respectively, we evaluate region-wise fractional anisotropy (FA), mean diffusivity, and principal eigenvector; region-wise cerebral spinal fluid volume fraction, intracellular volume fraction, and orientation dispersion index; bundle-wise shape, volume, FA, and length; and whole connectome correlation and maximized modularity, global efficiency, and characteristic path length.ResultsWe plot the variability in these measures at each level and find that it consistently increases with intrasession to intersession to interscanner to intersubject effects across all processing approaches and that sometimes interscanner variability can approach intersubject variability.ConclusionsThis study demonstrates the potential of MASiVar to more globally investigate DWI variability across multiple levels and processing approaches simultaneously and suggests harmonization between scanners for multisite analyses should be considered prior to inference of group differences on subjects.
A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients by phage display is binding to the ACE2-RBD interface and is tolerant to most known recently emerging RBD mutations
Authors: Bertoglio Federico , Fühner Viola , Ruschig Maximilian , Heine Philip Alexander , Abasi Leila , Klünemann Thomas , Rand Ulfert , Meier Doris , Langreder Nora , Steinke Stephan , Ballmann Rico , Schneider Kai-Thomas , Ralph Roth Kristian Daniel , Kuhn Philipp , Riese Peggy , Schäckermann Dorina , Korn Janin , Koch Allan , Chaudhry M. Zeeshan , Eschke Kathrin , Kim Yeonsu , Zock-Emmenthal Susanne , Becker Marlies , Scholz Margitta , Schmidt Garcia Moreira Gustavo Marçal , Wenzel Esther Veronika , Russo Giulio , Garritsen Hendrikus S.P. , Casu Sebastian , Gerstner Andreas , Roth Günter , Adler Julia , Trimpert Jakob , Hermann Andreas , Schirrmann Thomas , Dübel Stefan , Frenzel André , Van den Heuvel Joop , Čičin-Šain Luka , Schubert Maren , Hust Michael 
Published: December 2020

AbstractThe novel betacoranavirus SARS-CoV-2 causes a form of severe pneumonia disease, termed COVID-19 (coronavirus disease 2019). Recombinant human antibodies are proven potent neutralizers of viruses and can block the interaction of viral surface proteins with their host receptors. To develop neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor binding domain (RBD) of the S1 subunit of the viral spike (S) protein were selected by phage display. The selected antibodies were produced in the scFv-Fc format and 30 showed more than 80% inhibition of spike (S1-S2) binding to cells expressing ACE2, assessed by flow cytometry screening assay. The majority of these inhibiting antibodies are derived from the VH3-66 V-gene. The antibody STE90-C11 showed a sub nM IC50 in a plaque-based live SARS-CoV-2 neutralization assay. Thein vivoefficacy of the antibody was demonstrated in the Syrian hamster and in the hACE2 mice model using a silenced human IgG1 Fc part. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD was solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibtion of STE90-C11 is not blocked by many known RBD mutations including N439K, L452R, E484K or L452R+E484Q (emerging B.1.617). STE90-C11 derived human IgG1 with FcγR silenced Fc (COR-101) is currently undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.In BriefHuman antibodies were selected from convalescent COVID-19 patients using antibody phage display. The antibody STE90-C11 is neutralizing authentic SARS-CoV-2 virusin vitroandin vivoand the crystal structure of STE90-C11 in complex with SARS-CoV-2-RBD revealed that this antibody is binding in the RBD-ACE2 interface. S1 binding of STE90-C11 and inhibition of ACE2 binding is not blocked by many known RBD mutations.