bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy
Authors: Tourret Marie , Talvard-Balland Nana , Lambert Marion , Ben Youssef Ghada , Chevalier Mathieu F. , Bohineust Armelle , Yvorra Thomas , Morin Florence , Azarnoush Saba , Lantz Olivier , Dalle Jean-Hugues , Caillat-Zucman Sophie 
Published: April 2021

ABSTRACTBackgroundMucosal associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of anti - microbial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as “universal” cells would be a lack of alloreactive potential, which remains to be demonstrated.MethodsWe used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses.ResultsWe show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of conventional T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell mediated xenogeneic graft-versus-host disease (GVHD) in immunodeficient mice.ConclusionsAltogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity.
Interdental and subgingival microbiota may affect the tongue microbial ecology and oral malodour in health, gingivitis and periodontitis
Authors: Stephen Abish S. , Dhadwal Narinder , Nagala Vamshidhar , Gonzales-Marin Cecilia , Gillam David G. , Bradshaw David J. , Burnett Gary R. , Allaker Robert P. 
Published: April 2021

ABSTRACTBackground and ObjectiveOral malodour is often observed in gingivitis and chronic periodontitis patients, and the tongue microbiota is thought to play a major role in malodorous gas production, including Volatile Sulfur Compounds (VSCs) such as hydrogen sulfide (H2S) and methanethiol (CH3SH). This study aimed to examine the link between the presence of VSCs in mouth air (as a marker of oral malodour) and the oral bacterial ecology in the tongue and periodontal niches of healthy, gingivitis and periodontitis patients.MethodsParticipants were clinically assessed using plaque index, bleeding on probing (BOP) and periodontal probing depths, and VSC concentrations in their oral cavity measured using a portable gas chromatograph. Tongue scrapings, subgingival and interdental plaque were collected from healthy individuals (n=22), and those with gingivitis (n=14) or chronic periodontitis (n=15). The bacterial 16S rRNA gene region V3-V4 in these samples was sequenced and the sequences analysed using the Minimum Entropy Decomposition pipeline.ResultsElevated VSC concentrations and CH3SH:H2S were observed in periodontitis compared to health. Significant ecological differences were observed in the tongue microbiota of healthy subjects with high plaque scores compared to low plaque scores, suggesting a possible connection between the microbiota of the tongue and the periodontium and that key dysbiotic changes may be initiated in the clinically healthy who have higher dental plaque accumulation. Greater subgingival bacterial diversity was positively associated with H2S in mouth air. Periodontopathic bacteria known to be prolific VSC producers increased in abundance on the tongue associated with increased bleeding on probing (BOP) and total percentage of periodontal pockets >6mm, supporting the suggestion that the tongue may become a reservoir for periodontopathogens.ConclusionThis study highlights the importance of the periodontal microbiota in malodour and has detected dysbiotic changes in the tongue microbiota in periodontitis.
COMPARISON OF PERFORMANCE CHARACTERISTICS BETWEEN LATERAL FLOW, ELISA AND ELECTROCHEMILUMINESCENCE IMMUNOASSAYS FOR THE DETECTION OF SARS-COV-2 ANTIBODIES AMONG HEALTHCARE WORKERS
Authors: Shincy M R , Govindan Vandana , Sudhakar H H , Venkatesha V T , Padmapriya K , Ravikumar K L 
Published: April 2021

ABSTRACTBackgroundMedical professionals and researchers have been urging the need for wide and rapid testing of citizens in order to plan measures that can contain the spread of the virus. Antibody tests play an important role throughout the patient care pathway and are vital for the management and surveillance of the virus. Although RT-PCR is considered as the gold standard, serological tests based on antibodies are helpful for on-time detection. We performed one to one assessment of point-of-care lateral flow assay (POCTs), enzyme immunoassay (EIAs), electrochemiluminescence immunoassay (CLIA), to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody.Materials and Methods611 healthcare workers were recruited between November and December 2020 at Central Research Laboratory, KIMS. Collected serum samples were analysed according to manufacturer’s protocol. The Standard Q IgG/IgM combo assay, Anti-SARS CoV-2 Human IgG ELISA, and the Elecsys® to measure the IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ResultsThe kits displayed a sensitivity of 61.2%,79.5%, 91.8% and specificity of 61.7%,64.1%,80.2% for the Standard Q IgG/IgM combo assay, Anti-SARS CoV-2 Human IgG ELISA, and the Elecsys® in order.ConclusionOur results indicate high sensitivity and specificity for the Elecsys® assay compared to Anti-SARS CoV-2 Human IgG ELISA, the Standard Q IgG/IgM combo assay.
TranSyT, an innovative framework for identifying transport systems
Authors: Lagoa Davide , Faria José P. , Liu Filipe , Cunha Emanuel , Henry Christopher S. , Dias Oscar 
Published: April 2021

ABSTRACTThe importance and rate of development of genome-scale metabolic models have been growing for the last years, increasing the demand for software solutions that automate several steps of this process. However, since TRIAGE’s release, software development for automatic integration of transport reactions into models has stalled. Here we present the Transport Systems Tracker (TranSyT), the next iteration of TRIAGE. Unlike its predecessor,TranSyTdoes not rely on manual curation to expand its internal database, derived from highly-curated records retrieved from the Transporters Classification Database and complemented with information from other data sources.TranSyTcompiles information regarding transporters families, transport proteins, and derives reactions into its internal database, making it available for rapid annotation of complete genomes. All transport reactions have GPR associations and can be exported with identifiers from four different metabolite databases.TranSyTis currently available as a plugin formerlinv4.0 and an app for KBase.
Movement-Preceding Neural Activity under Parametrically Varying Levels of Time Pressure
Authors: Trovò Bianca , Visser Yvonne , İşcan Zafer , Schurger Aaron 
Published: April 2021

AbstractSelf-initiated movements are known to be preceded by the readiness potential or RP, a gradual increase in surface-negativity of cortical potentials that can begin up to 1 second or more before movement onset. The RP has been extensively studied for decades, and yet we still lack a clear understanding of its functional role. Attempts to model the RP as an accumulation-to-bound process suggest that this signal is a by-product of time-locking to crests in neural noise rather than the outcome of a pre-conscious decision to initiate a movement. One parameter of the model accounts for the imperative to move now, with cued movements having a strong imperative and purely spontaneous movements having no imperative. Two different variants of the model have been proposed, and both predict a decrease in the (negative) amplitude of the early RP as the imperative grows stronger. In order to test this empirically, we conducted an experiment where subjects produced self-initiated movements under varying levels of time pressure, and we investigated the amplitude, shape, and latency of the RP as a function of the imperative to move, operationalised as a time limit. We identified distinct changes in the amplitude of the early RP that grew non-linearly as the time limit grew shorter. Thus these data did not support the prediction made by the model. In addition, our results confirm that the shape of the RP is not stereotypically negative, being either positive or absent in about half of the subjects.
Nopp140-chaperoned 2’-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity
Authors: Bizarro Jonathan , Deryusheva Svetlana , Wacheul Ludivine , Gupta Varun , Ernst Felix G.M. , Lafontaine Denis L.J. , Gall Joseph G. , Meier U. Thomas 
Published: April 2021

ABSTRACTSpliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB) specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at some 80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2’-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.
Cerebellar Neuronal Dysfunction Accompanies Early Motor Symptoms in Spinocerebellar Ataxia Type 3
Authors: Mayoral-Palarz Kristin , Neves-Carvalho Andreia , Maciel Patrícia , Khodakhah Kamran 
Published: April 2021

AbstractSpinocerebellar Ataxia Type 3 (SCA3) is an adult-onset, progressive ataxia. SCA3 presents with ataxia before any gross neuropathology. A feature of many cerebellar ataxias is aberrant cerebellar output that contributes to motor dysfunction. We examined whether abnormal cerebellar output was present in the CMVMJD135 SCA3 mouse model and, if so, whether it correlated with the disease onset and progression.In vivorecordings showed that the activity of deep cerebellar nuclei neurons, the main output of the cerebellum, was altered. The aberrant activity correlated with the onset of ataxia. However, although the severity of ataxia increased with age, the severity of the aberrant cerebellar output was not progressive. The abnormal cerebellar output, however, was accompanied with non-progressive abnormal activity of their upstream synaptic inputs, the Purkinje cells.In vitrorecordings indicated that alterations in both intrinsic Purkinje cell pacemaking and in their synaptic inputs contributed to abnormal Purkinje cell activity. These findings implicate abnormal cerebellar physiology as an early, consistent contributor to pathophysiology in SCA3, and suggest that the aberrant cerebellar output could be an appropriate therapeutic target in SCA3.Summary StatementIn a mouse model of Spinocerebellar ataxia type 3 aberrant cerebellar physiology is apparent early in disease, before overt neuronal pathology or neuronal death.
Type I interferon responsive microglia shape cortical development and behavior
Authors: Escoubas Caroline C. , Dorman Leah C. , Nguyen Phi T. , Lagares-Linares Christian , Nakajo Haruna , Anderson Sarah R. , Cuevas Beatriz , Vainchtein Ilia D. , Silva Nicholas J. , Xiao Yinghong , Lidsky Peter V. , Wang Ellen Y. , Taloma Sunrae E. , Nakao-Inoue Hiromi , Schwer Bjoern , Andino Raul , Nowakowski Tomasz J. , Molofsky Anna V. 
Published: April 2021

SummaryMicroglia are brain resident phagocytes that can engulf synaptic components and extracellular matrix as well as whole neurons. However, whether there are unique molecular mechanisms that regulate these distinct phagocytic states is unknown. Here we define a molecularly distinct microglial subset whose function is to engulf neurons in the developing brain. We transcriptomically identified a cluster of Type I interferon (IFN-I) responsive microglia that expanded 20-fold in the postnatal day 5 somatosensory cortex after partial whisker deprivation, a stressor that accelerates neural circuit remodeling.In situ, IFN-I responsive microglia were highly phagocytic and actively engulfed whole neurons. Conditional deletion of IFN-I signaling (Ifnar1fl/fl) in microglia but not neurons resulted in dysmorphic microglia with stalled phagocytosis and an accumulation of neurons with double strand DNA breaks, a marker of cell stress. Conversely, exogenous IFN-I was sufficient to drive neuronal engulfment by microglia and restrict the accumulation of damaged neurons. IFN-I deficient mice had excess excitatory neurons in the developing somatosensory cortex as well as tactile hypersensitivity to whisker stimulation. These data define a molecular mechanism through which microglia engulf neurons during a critical window of brain development. More broadly, they reveal key homeostatic roles of a canonical antiviral signaling pathway in brain development.
Evaluation of data-driven MEG analysis approaches for the extraction of fMRI resting state networks
Authors: Pelzer Esther Annegret , Sharma Abhinav , Florin Esther 
Published: April 2021

AbstractThe electrophysiological basis of resting state networks (RSN) is still under debate. In particular, no principled mechanism has been determined that is capable of explaining all RSN equally well. While magnetoencephalography (MEG) and electroencephalography (EEG) are the methods of choice to determine the electrophysiological basis of RSN, no standard analysis pipeline of RSN yet exists. In this paper, we compare the two main existing data-driven analysis strategies for extracting resting state networks from MEG data. The first approach extracts RSN through an independent component analysis (ICA) of the Hilbert envelope in different frequency bands. The second approach uses phase –amplitude coupling to determine the RSN. To evaluate the performance of these approaches, we compare the MEG-RSN to the functional magnetic resonance imaging (fMRI)-RSN from the same subjects.Overall, it was possible to extract the canonical fMRI RSN with MEG. The approach based on phase-amplitude coupling yielded the best correspondence to the fMRI-RSN. The Hilbert envelope-ICA produced different dominant frequency-bands underlying RSN for different ICA runs, suggesting the absence of a single dominant frequency underlying the RSN. Our results also suggest that individual RSN are not characterized by one single dominant frequency. Instead, the resting state networks seem to be based on a combination of the delta/theta phase and gamma amplitude.
A model of naturalistic decision making in preference tests
Authors: Ksander John , Katz Donald B , Miller Paul 
Published: April 2021

AbstractDecisions as to whether to continue with an ongoing activity or to switch to an alternative are a constant in an animal’s natural world, and in particular underlie foraging behavior and performance in food preference tests. Stimuli experienced by the animal both impact the choice and are themselves impacted by the choice, in a dynamic back and forth. Here, we present model neural circuits, based on spiking neurons, in which the choice to switch away from ongoing behavior instantiates this back and forth, arising as a state transition in neural activity. We analyze two classes of circuit, which differ in whether state transitions result from a loss of hedonic input from the stimulus (an “entice to stay” model) or from aversive stimulus input (a “repel to leave” model). In both classes of model, we find that the mean time spent sampling a stimulus decreases with increasing value of the alternative stimulus, a fact that we linked to the inclusion of depressing synapses in our model. The competitive interaction is much greater in “entice to stay” model networks, which has qualitative features of the marginal value theorem, and thereby provides a framework for optimal foraging behavior. We offer suggestions as to how our models could be discriminatively tested through the analysis of electrophysiological and behavioral data.Author summaryMany decisions are of the ilk of whether to continue sampling a stimulus or to switch to an alternative, a key feature of foraging behavior. We produce two classes of model for such stay-switch decisions, which differ in how decisions to switch stimuli can arise. In an “entice-to-stay” model, a reduction in the necessary positive stimulus input causes switching decisions. In a “repel-to-leave” model, a rise in aversive stimulus input produces a switch decision. We find that in tasks where the sampling of one stimulus follows another, adaptive biological processes arising from a highly hedonic stimulus can reduce the time spent at the following stimulus, by up to ten-fold in the “entice-to-stay” models. Along with potentially observable behavioral differences that could distinguish the classes of networks, we also found signatures in neural activity, such as oscillation of neural firing rates and a rapid change in rates preceding the time of choice to leave a stimulus. In summary, our model findings lead to testable predictions and suggest a neural circuit-based framework for explaining foraging choices.
Biomolecular mechanisms for signal differentiation
Authors: Alexis Emmanouil , Schulte Carolin CM , Cardelli Luca , Papachristodoulou Antonis 
Published: April 2021

AbstractCells can sense temporal changes of molecular signals, allowing them to predict environmental vari-ations and modulate their behaviour. This paper elucidates the underlying biomolecular mechanisms of time derivative computation, facilitating the design of reliable synthetic differentiator devices for a variety of applications, ultimately expanding our understanding of cell behaviour. In particular, we describe and analyse three alternative biomolecular topologies that work as signal differentiators of high accuracy to arbitrary input signals around their nominal operation. We propose strategies to preserve their performance even in the presence of high-frequency input signal components, which are detrimental to the performance of most differentiators. We found that the core of the proposed topologies appears in natural regulatory networks and we further discuss their biological relevance. The simple structure of our designs makes them promising tools for realizing derivative control action in synthetic biology.
Hybridization and cryptic speciation in the Tropical Eastern Pacific octocoral genusPacifigorgia
Authors: Poliseno Angelo , Breedy Odalisca , Guzman Hector M. , Vargas Sergio 
Published: April 2021

AbstractThe shallow waters of the Tropical Eastern Pacific (TEP) harbor a species-rich octocoral fauna, with seven genera and 124 octocoral species described to date for the region. Of these lineages,Pacifigorgia, with 35 species, is by far the most speciose and abundant shallow-water octocoral occurring in the region. The speciation mechanisms resulting in this remarkable diversity remain speculative, despite the extensive taxonomic and molecular systematic research conducted so far in the TEP. Using genome-wide SNP markers, we provide evidence for hybridization and extensive cryptic speciation inPacifigorgia, suggesting that the genus’ diversity has been underestimated by traditional and molecular systematic research. Our study highlights the difficulties faced by both traditional taxonomy and single-marker based molecular approaches to characterize octocoral diversity and evolution, and the role genome-wide molecular studies coupled to morphological research play to advance our understanding of this group.
Climate trends and behavior of an avian forest specialist in central Amazonia indicate thermal stress during the dry season
Authors: Jirinec Vitek , Rutt Cameron L. , Elizondo Elisa C. , Rodrigues Patricia F. , Stouffer Philip C 
Published: April 2021

AbstractRainforest loss threatens terrestrial insectivorous birds throughout the world’s tropics. Recent evidence shows these birds to be declining in undisturbed Amazonian rainforest, possibly due to climate change. Here, we first addressed whether Amazonian terrestrial insectivores were exposed to climate change using 38 years of climate data. We found that climate has changed in central Amazonia, especially in the dry season, which was ∼1.3°C hotter and 21% drier in 2019 than in 1981. Second, to test whether birds actively avoided hot and dry conditions, we used field sensors to identify ambient extremes and prospective microclimate refugia within undisturbed rainforest from 2017 – 2019. Simultaneously, we examined how tagged Black-faced Anthrushes (Formicarius analis) used this space. We collected 1.4 million field measurements quantifying ambient conditions in the forest understory, including along elevation gradients. For 11 birds, we obtained GPS locations to test whether birds adjusted their shelter use (n= 2,724) or elevation (n= 640) across seasonal and daily cycles. For four additional birds, we collected >180,000 light and temperature readings to assess exposure. Field measurements in the modern landscape revealed that temperature was higher in the dry season and highest on plateaus. Thus, low-lying areas were relatively buffered, providing microclimate refugia during hot afternoons in the dry season. At those times, birds entered shelters and shifted downslope, reducing their thermal exposure by 50%. Because climate change intensifies the hot, dry conditions that antthrushes avoid, our results are consistent with the hypothesis that climate change lowers habitat quality for terrestrial insectivores. This sensitivity may be related to their declines within ‘undisturbed’ Amazonian rainforest.