bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Airy beam Light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids
Authors: Adhya Dwaipayan , Chennell George , Crowe James , Valencia-Alarcón Eva P. , Seyforth James , Honsy Neveen , Yasvoina Marina V. , Forster Robert , Baron-Cohen Simon , Vernon Anthony C. , Sriavstava Deepak. P. 
Published: June 2020

AbstractBackgroundThe inability to observe relevant biological processesin vivosignificantly restricts human neurodevelopmental research. Advances in appropriatein vitromodel systems, including patient-specific human brain organoids and human Cortical Spheroids (hCSs) offer a pragmatic solution to this issue. In particular, hCSs are an accessible method of generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes. These neurogeneic niches give rise to neural progenitors that subsequently differentiate into neurons. Atypical formation of these structures has been associated with neurodevelopmental disorders such as autism spectrum conditions, from studies of patient-specific human induced pluripotent stem cells grown as 2D cultures. Thus far however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hSC or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points.ResultsConventional approaches to imaging hCS by confocal microscopy were limited in their ability to image effectively into intact spheroids. Conversely, volumetric acquisition by ALSM offered superior imaging through intact, non-clarified,in vitrotissues, in both speed and resolution as compared to conventional confocal imaging systems. Furthermore, optimised immunohistochemistry and optical clearing of hCSs afforded improved imaging at depth. This permitted visualization of the morphology of the inner lumen of neural rosettes.ConclusionWe present an optimized methodology that takes advantage of an ALSM system that can rapidly image intact 3D brain organoids at high resolution while retaining a large field of view. This imaging modality can be applied to both non-cleared and clearedin vitrohuman brain spheroids derived from hiPSCs for precise examination of their internal 3D structures. Furthermore, this process represents a rapid, highly efficient method to examine and quantify in 3D the formation of key structures required for the coordination of neurodevelopmental processes in both health and disease states. We posit that this approach would facilitate investigation of human neurodevelopmental processes.
Repeated stimulation or tonic-signaling chimeric antigen receptors drive regulatory T cell exhaustion
Authors: Lamarche Caroline , Novakovsky German E. , Qi Christopher N. , Weber Evan W. , Mackall Crystal L. , Levings Megan K 
Published: June 2020

AbstractRegulatory T cell (Treg) therapy is a promising approach to improve outcomes in transplantation and autoimmunity. In conventional T cell therapy, chronic stimulation can result in poorin vivofunction, a phenomenon termed exhaustion. Whether or not Tregs are also susceptible to exhaustion, and if so, if this would limit their therapeutic effect, was unknown. We studied how two methods which induce conventional T cell exhaustion – repetitive stimulation or expression of a tonic-signaling chimeric antigen receptor (CAR) – affect human Tregs. With each repetitive polyclonal stimulation Tregs progressively acquired an exhausted phenotype, and became less suppressivein vitro. Tregs expressing a tonic-signaling CAR rapidly acquired an exhausted phenotype and had major changes in their transcriptome and metabolism. Although tonic-signaling CAR-Tregs remained stable and suppressivein vitro, they lostin vivofunction, as tested in a model of xenogeneic graft-versus-host disease. The finding that human Tregs are susceptible to exhaustion has important implications for the design of Treg adoptive immunotherapy strategies.
Stabilizing selection of seasonal influenza receptor binding in populations with partial immunity
Authors: Hay James A. , Junus Alvin , Riley Steven , Yuan Hsiang-Yu 
Published: June 2020

AbstractMutations that alter cellular receptor binding of influenza hemagglutinin (HA) have profound effects on immune escape. Despite its high mutation rate, it is not fully understood why human influenza HA displays limited antigenic diversity across circulating viruses. We applied phylogenetic analysis and phylodynamic modeling to understand the evolutionary and epidemiological effects of binding avidity adaptation in humans using net charge as a marker for receptor binding avidity. Using 686 human influenza A/H3N2 HA sequences, we found that HA net charge followed an age-specific pattern. Phylogenetic analysis suggested that many binding variants have reduced fitness. Next, we developed an individual-based disease dynamic model embedded with within-host receptor binding adaptation and immune escape in a population with varied partial immunity. The model showed that mean binding avidity was unable to adapt to values that maximized transmissibility due to competing selective forces between within- and between-host levels. Overall, we demonstrated stabilizing selection of virus binding in a population with increasing partial immunity. These findings have potential implications in understanding the evolutionary mechanisms that determine the intensity of seasonal influenza epidemics.
Elevated Neurokinin 1-Receptor Expression in uterine products of conception is associated with first trimester Miscarriages
Authors: Mehboob Riffat , Gilani Syed Amir , Hassan Amber , Tirmazi Adeel Haider , Ahmad Fridoon Jawad , Akram Javed 
Published: June 2020

AbstractBackgroundMiscarriage is a common complication of early pregnancy, mostly occurring in first trimester. However, the etiological factors, prognostic and diagnostic biomarkers are not well known. Neurokinin-1 Receptor (NK-1R) is a receptor of tachykinin peptide, Substance P (SP) and has a role in various pathological conditions, cancers but it’s association with miscarriages and significance as a clinicopathological parameter is not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception. Role of NK-1R is not known in miscarriages.Materials and MethodsNK-1R expression was assessed in products of conception by immunohistochemistry. Protein expression was evaluated using the nuclear labelling index (%).ResultsTen human products of conception tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of POCs. NK-1R expression showed no notable differences among different cases of miscarriages irrespective of the mother’s age and gestational age at which the event occurred.ConclusionsExpression of NK-1R was similar in all the cases and it was intense. It shows that dysregulation of NK-1R along with its ligand Substance P might be involved in miscarriages. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time, the expression and localization of NK-1R in products of conception. We suggest NK-1R antagonist in addition to the Immunoglobulins and Human chorionic gonadotropin, to diagnose and treat spontaneous miscarriages.
The evolution of seasonal migration and the slow-fast continuum of life history in birds
Authors: Winger Benjamin M. , Pegan Teresa M. 
Published: June 2020

AbstractSeasonal migration is a widespread adaptation in environments with predictable periods of resource abundance and scarcity. Migration is frequently associated with high mortality, suggesting that migratory species live on the “fast” end of the slow-fast continuum of life history. However, few interspecific comparative studies have tested this assumption and prior assessments have been complicated by environmental variation among breeding locations. We evaluate how migration distance influences the tradeoff between reproduction and survival in 45 species of mostly passerine birds that breed sympatrically in North American boreal forests but migrate to a diversity of environments and latitudes for the northern winter. We find, after accounting for mass and phylogeny, that longer distance migrations to increasingly amenable winter environments are correlated with reduced annual reproductive output, but also result in increased adult survival compared to shorter-distance migrations. Non-migratory boreal species have life history parameters more similar to long-distance migrants than to shorter-distance migrants. These results suggest that long-distance migration and other highly specialized strategies for survival in seasonal environments impose selection pressures that both confer and demand high adult survival rates. That is, owing to the reproductive cost of long-distance migration, this strategy can only persist if balanced by high adult survival. Our results reveal migratory distance as a fundamental life history parameter that predicts, and is inextricable from, the balance of survival and reproduction. Our study further provides evolutionary context for understanding the annual cycle demography of migratory species and the strategies long-distance migrants use to maximize survival on their journeys.
Estimating the state of the Covid-19 epidemic in France using a non-Markovian model
Authors: Forien Raphaël , Pang Guodong , Pardoux Étienne 
Published: June 2020

AbstractIn this paper, we use a deterministic non-Markovian epidemic model to estimate the state of the Covid-19 epidemic in France. This model allows us to consider realistic distributions for the exposed and infectious periods in a SEIR model, contrary to standard ODE models which only consider exponentially distributed exposed and infectious periods. We present theoretical results linking the (unobserved) parameters of the model to various quantities which are more easily measured during the early stages of an epidemic. We also stress the main quantitative differences between the non-Markovian and the Markovian (ODE) model. We then apply these results to estimate the state of the Covid-19 epidemic in France by analyzing three regions: the Paris region, the northeast regions and the rest of the country, based on current knowledge on the infection fatality ratio and the exposed and infectious periods distributions for Covid-19. Our analysis is based on the hospital data published daily by Santé Publique France (daily hospital admissions, intensive care unit admissions and hospital deaths).
Facilitation of neural responses to targets moving against optic flow
Authors: Nicholas Sarah , Nordström Karin 
Published: June 2020

AbstractFor the human observer, it can be difficult to follow the motion of small objects, especially when they move against background clutter. In contrast, insects efficiently do this, as evidenced by their ability to capture prey, pursue conspecifics, or defend territories, even in highly textured surrounds. We here recorded from target selective descending neurons (TSDNs) which likely subserve these impressive behaviors. To simulate the type of background optic flow that would be generated by the pursuer’s own movements through the world, we used the coherent motion of a perspective distorted sparse dot field. We show that hoverfly TSDN responses to target motion are suppressed when such background optic flow moves in the same direction as the target. Indeed, the neural responses are strongly attenuated against both translational sideslip as well as rotational yaw. More strikingly, we show that TSDNs are facilitated by background optic flow in the opposite direction to the target, if the target moves horizontally. Furthermore, we show that a small, frontal spatial window of background optic flow is enough to fully facilitate or attenuate TSDN responses to target motion. We argue that the TSDN response facilitation could be beneficial in modulating corrective turns during target pursuit.Significance statementTarget detection in visual clutter is a difficult computational task that insects, with their poor resolution compound eyes and small brains, do successfully and with extremely short behavioral delays. We here show that the responses of target selective descending neurons are attenuated by background motion in the same direction as target motion, but facilitated by opposite direction background motion. This finding is important for understanding conspecific pursuit behavior, since these descending neurons likely control behavioral output. The facilitation that we describe would come into effect if the hoverfly is subjected to background motion in one direction, but the target it is pursuing moves in the opposite direction, and could therefore be used to modulate gaze stabilizing corrective turns.
Amplitude of high frequency oscillations as a biomarker of the seizure onset zone
Authors: Charupanit Krit , Sen-Gupta Indranil , Lin Jack J , Lopour Beth A 
Published: June 2020

AbstractObjectiveStudies of high frequency oscillations (HFOs) in epilepsy have primarily tested the HFO rate as a biomarker of the seizure onset zone (SOZ), but the rate varies over time and is not robust for all individual subjects. As an alternative, we tested the performance of HFO amplitude as a potential SOZ biomarker using two automated detection algorithms.MethodHFOs were detected in intracranial electroencephalogram (iEEG) from 11 patients using a machine learning algorithm and a standard amplitude-based algorithm. For each detector, SOZ and non-SOZ channels were classified using the rate and amplitude of high frequency events, and performance was compared using receiver operating characteristic curves.ResultsThe amplitude of detected events was significantly higher in SOZ. Across subjects, amplitude more accurately classified SOZ/non-SOZ than rate (higher values of area under the ROC curve and sensitivity, and lower false positive rates). Moreover, amplitude was more consistent across segments of data, indicated by lower coefficient of variation.ConclusionAs an SOZ biomarker, HFO amplitude offers advantages over HFO rate: it exhibits higher classification accuracy, more consistency over time, and robustness to parameter changes.SignificanceThis biomarker has the potential to increase the generalizability of HFOs and facilitate clinical implementation as a tool for SOZ localization.
SeedExtractor: an open-source GUI for seed image analysis
Authors: Zhu Feiyu , Paul Puneet , Hussain Waseem , Wallman Kyle , Dhatt Balpreet K , Sandhu Jaspreet , Irvin Larissa , Morota Gota , Yu Hongfeng , Walia Harkamal 
Published: June 2020

ABSTRACTAccurate measurement of seed size parameters is essential for both: breeding efforts□aimed at□enhancing yields and basic research□focused on discovering genetic components that regulate seed size. To address this need, we have developed an open-source graphical user interface (GUI) software,SeedExtractorthat□determines seed size and shape (including area, perimeter, length, width, circularity, and centroid), and seed color with capability to process a large number of images in a time-efficient manner. In this context, our application takes ∼2 seconds for analyzing an image, i.e. significantly less compared to the other tools. As this software is open-source, it can be modified by users□to serve more specific needs. The adaptability ofSeedExtractorwas demonstrated by analyzing scanned seeds from multiple crops. We further validated the utility of this application by analyzing mature-rice seeds from 231 accessions in Rice Diversity Panel 1. The derived seed-size traits, such as seed length, width, were subjected to genome-wide association analysis. We identified well-known loci for regulating seed length (GS3) and width (qSW5/GW5) in rice, which demonstrated the accuracy of this application to extract seed phenotypes and accelerate trait discovery. In summary, we present a publicly available application that can be used to determine key yield-related traits in crops.HIGHLIGHTSeedExtractoris an open-source application designed to accurately measure seed size and seed color in a time-efficient manner for a wide variety of plant species.
Interconnected assembly factors regulate the biogenesis of mitoribosomal large subunit
Authors: Tobiasson Victor , Gahura Ondřej , Aibara Shintaro , Baradaran Rozbeh , Zíková Alena , Amunts Alexey 
Published: June 2020

AbstractMitoribosomes consist of ribosomal RNA and protein components, coordinated assembly of which is critical for function. We used mitoribosomes with reduced RNA and increased protein mass fromTrypanosoma brucei, to provide insights into the biogenesis of mitoribosomal large subunit. Structural characterisation of a stable assembly intermediate revealed 22 assembly factors, some of which are also encoded in mammalian genomes. The assembly factors form a protein network that spans over 180 Å, shielding the ribosomal RNA surface. The entire central protuberance and L7/L12 stalk are not assembled, and require removal of the factors and remodeling of the mitoribosomal proteins to become functional. The conserved proteins GTPBP7 and mt-EngA are bound together at the subunit interface in proximity to the peptidyl transferase center. A mitochondrial acyl-carrier protein plays a role in docking the L1 stalk which needs to be repositioned during maturation. Additional enzymatically deactivated factors scaffold the assembly, while the exit tunnel is blocked. Together, the extensive network of the factors stabilizes the immature sites and connects the functionally important regions of the mitoribosomal large subunit.
Variability in Fruit Yield and Quality of Genetically Diverse Tomato Cultivars in Response to Different Biochars
Authors: Tenic Elvir , Isaac Daylen , Ghogare Rishikesh , Dhingra Amit 
Published: June 2020

AbstractBackgroundIntensive agricultural practices have reduced soil health thereby negatively impacting crop yields. There is a need to maintain healthy soils and restore marginal lands to ensure efficient food production. Biochar, a porous carbon-rich material generated from pyrolysis of various feedstock sources is receiving attention as a soil amendment that has the potential to restore soil organic carbon content and also enhance crop yields. However, the physical and chemical properties of biochar are influenced by pyrolysis parameters. These in turn determine its interaction with the soil, thereby influencing its biological properties in terms of impact on soil microcosm and plant productivity. While most studies report the evaluation of one biochar and a single plant cultivar, the role of the plant’s genetic background in responding to biochar as a soil amendment remains unanswered. The impact of six distinct biochars on agronomic performance and fruit quality of three genetically diverse tomato (Solanum lycopersicum) cultivars was evaluated to test the hypotheses that 1) biochars derived from different feedstock sources would produce unique phenotypes in a single cultivar of tomato, and 2) single feedstock-derived BC would produce different phenotypes in each of the three tomato cultivars.ResultsDifferent biochars impacted shoot dry weight, total fruit weight, and yield per plant in each cultivar differently. Both positive and negative effects were observed depending on the biochar-cultivar combination. In ‘Oregon Spring’, Ryegrass straw and CoolTerra biochar enhanced yield. In ‘Heinz’, an increase in fruit weight and citric acid was observed with several of the biochars. In ‘Cobra’, improved yields were accompanied by reduction in fruit quality parameters. Both hypotheses were supported by the data.ConclusionsThis study demonstrated that the genetic background of a plant is an important variable in determining the outcome of using biochar as a soil amendment. Strategies for application of biochar in agricultural production should consider the variables of soil type, feedstock source, pyrolysis parameters and plant genetic background for enhancing crop productivity and carbon sequestration.
High-performance pipeline for MutMap and QTL-seq
Authors: Sugihara Yu , Young Lester , Yaegashi Hiroki , Natsume Satoshi , Shea Daniel J. , Takagi Hiroki , Booker Helen , Innan Hideki , Terauchi Ryohei , Abe Akira 
Published: June 2020

AbstractBulked segregant analysis implemented in MutMap and QTL-seq is a powerful and efficient method to identify agronomically important loci. However, the previous pipelines were not user-friendly to install and run. Here, we describe new pipelines for MutMap and QTL-seq. These updated pipelines are approximately 5-8 times faster than the previous pipeline, are easier for novice users to use and can be easily installed through bioconda with all dependencies.
Deglutarylation of GCDH by SIRT5 controls lysine metabolism in mice
Authors: Bhatt Dhaval P. , Mills C. Allie , Anderson Kristin A. , Henriques Bárbara J. , Lucas Tânia G. , Francisco Sara , Liu Juan , Ilkayeva Olga R. , Adams Alexander E. , Kulkarni Shreyas R. , Backos Donald S. , Grimsrud Paul A. , Gomes Cláudio M. , Hirschey Matthew D. 
Published: June 2020

ABSTRACTA wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be non-enzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme Sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH). We show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We then demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a model whereby a feedback loop exists within the lysine/tryptophan oxidation pathway, in which glutaryl-CoA is produced, in turn inhibiting GCDH functionviaglutaryl modification of GCDH lysine residues, and can be relieved by SIRT5 deacylation activity.