bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage disequilibrium and population structure in a core collection ofBrassica napus(L.)
Authors: Rahman Mukhlesur , Hoque Ahasanul , Roy Jayanta 
Published: April 2021

AbstractEstimation of genetic diversity in rapeseed/canola is important for sustainable breeding program to provide an option for the development of new breeding lines. The objective of this study was to elucidate the patterns of genetic diversity within and among different structural groups, and measure the extent of linkage disequilibrium (LD) of 383 globally distributed rapeseed/canola germplasm using 8,502 single nucleotide polymorphism (SNP) markers. The germplasm accessions were divided into five subpopulations (P1 to P5) with obvious geographic and growth habit-related patterns. All subpopulations showed moderate genetic diversity (averageH= 0.22 andI= 0.34). The pairwiseFstcomparison revealed a great degree of divergence (Fst> 0.24) between most of the combinations. The rutabaga type showed highest divergence with spring and winter types. Higher divergence was also found between winter and spring types. Overall, mean linkage disequilibrium was 0.03 and it decayed to its half maximum within < 45 kb distance for whole genome. The LD decay was slower in C genome (< 93 kb), relative to the A genome (< 21 kb) which was confirmed by availability of larger haplotype blocks in C genome than A genome. To maximize genetic gain, hybridization between rutabaga and other types are potentially the best option. Hybridization between spring and winter, semi-winter type is also helpful to maximize the diversity in subsequent populations. Low genetic differentiation between both spring type subpopulations (P4 and P3) will accelerate favorable allele accumulation for specific traits in elite lines. The Neighbor-Joining tree and kinship matrix will assist to identify distantly related genotypes from subpopulations to utilize in hybridization. The low levels of LD and population structure make the core collection an important resource for association mapping efforts to identify genes useful in crop improvement as well as for selection of parents for hybrid breeding.
A Toolbox and Crowdsourcing Platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE)
Authors: Soghoyan Gurgen , Ledovsky Alexander , Nekrashevich Maxim , Martynova Olga , Polikanova Irina , Portnova Galina , Rebreikina Anna , Sysoeva Olga , Sharaev Maxim 
Published: April 2021

ABSTRACTIndependent Component Analysis (ICA) is a conventional approach to exclude non-brain signals such as eye-movements and muscle artifacts from electroencephalography (EEG). Due to other possible EEG contaminations, a rejection of independent components (ICs) is usually performed in semiautomatic mode and requires experts’ involvement. Noteworthy, as also revealed by our study, experts’ opinion about the nature of a component often disagrees highlighting the need to develop a robust and sustainable automatic system for EEG ICs classification. The current article presents a toolbox and crowdsourcing platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE) available via linkhttp://alice.adase.org/. The ALICE toolbox aims to build a sustainable algorithm not only to remove artifacts but also to find specific patterns in EEG signals using ICA decomposition based on accumulated experts’ knowledge.The difference from previous toolboxes is that the ALICE project will accumulate different benchmarks based on crowdsourced visual labeling of ICs collected from publicly available and in-house EEG recordings. The choice of labeling is based on estimation of IC time-series, IC amplitude topography and spectral power distribution. The platform allows supervised ML model training and re-training on available data subsamples for better performance in specific tasks (i.e. movement artifact detection in healthy or autistic children). Also, current research implements the novel strategy for consentient labeling of ICs by several experts. The provided baseline model shows that it can be used not only for detection of noisy IC but also for automatic identifications of components related to the functional brain oscillations such as alpha and mu-rhythm.The ALICE project implies the creation and constant replenishment of the IC database, which will be used for continuous improvement of ML algorithms for automatic labeling and extraction of non-brain signals from EEG. The toolbox and current dataset are open-source and freely available to the researcher community.
Host factors drive the within-host competition between highly and low pathogenic H5N8 avian influenza viruses
Authors: Bessière Pierre , Figueroa Thomas , Coggon Amelia , Foret-Lucas Charlotte , Houffschmitt Alexandre , Fusade-Boyer Maxime , Dupré Gabriel , Guérin Jean-Luc , Delverdier Maxence , Volmer Romain 
Published: April 2021

ABSTRACTHighly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8LPincreased H5N8HPreplication and pathogenesis. By contrast, the H5N8LPantagonized H5N8HPreplication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8LP, which correlated with H5N8HPinhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variants interactions in viral evolution.
Mutations in the B.1.1.7 SARS-CoV-2 spike protein reduce receptor-binding affinity and induce a flexible link to the fusion peptide
Authors: Socher Eileen , Conrad Marcus , Heger Lukas , Paulsen Friedrich , Sticht Heinrich , Zunke Friederike , Arnold Philipp 
Published: April 2021

AbstractThe B.1.1.7 variant of the SARS-CoV-2 virus shows enhanced infectiousness over the wild type virus, leading to increasing patient numbers in affected areas. A number of single amino acid exchanges and deletions within the trimeric viral spike protein characterize this new SARS-CoV-2 variant. Crucial for viral entry into the host cell is the interaction of the spike protein with the cell surface receptor angiotensin-converting enzyme 2 (ACE2) as well as integration of the viral fusion peptide into the host membrane. Respective amino acid exchanges within the SARS-CoV-2 variant B.1.1.7 affect inter-monomeric contact sites within the spike protein (A570D and D614G) as well as the ACE2-receptor interface region (N501Y), which comprises the receptor-binding domain (RBD) of the viral spike protein. However, the molecular consequences of mutations within B.1.1.7 on spike protein dynamics and stability, the fusion peptide, and ACE2 binding are largely unknown. Here, molecular dynamics simulations comparing SARS-CoV-2 wild type with the B.1.1.7 variant revealed inter-trimeric contact rearrangements, altering the structural flexibility within the spike protein trimer. In addition to reduced flexibility in the N-terminal domain of the spike protein, we found increased flexibility in direct spatial proximity of the fusion peptide. This increase in flexibility is due to salt bridge rearrangements induced by the D614G mutation in B.1.1.7 found in pre- and post-cleavage state at the S2’ site. Our results also imply a reduced binding affinity for B.1.1.7 with ACE2, as the N501Y mutation restructures the RBD-ACE2 interface, significantly decreasing the linear interaction energy between the RBD and ACE2.Our results demonstrate how mutations found within B.1.1.7 enlarge the flexibility around the fusion peptide and change the RBD-ACE2 interface, which, in combination, might explain the higher infectivity of B.1.1.7. We anticipate our findings to be starting points for in depth biochemical and cell biological analyses of B.1.1.7, but also other highly contagious SARS-CoV-2 variants, as many of them likewise exhibit a combination of the D614G and N501Y mutation.
Septin-microtubule association requires a MAP-like motif unique to Sept9 isoform 1 embedded into septin octamers
Authors: Kuzmić Mira , Linares Gerard Castro , Fialová Jindřiška Leischner , Iv François , Salaün Danièle , Llewellyn Alex , Gomes Maxime , Belhabib Mayssa , Liu Yuxiang , Asano Keisuke , Tachibana Taro , Koenderink Gijsje , Badache Ali , Mavrakis Manos , Verdier-Pinard Pascal 
Published: April 2021

AbstractSeptins, a family of GTP-binding proteins assembling into higher order structures, interface with the membrane, actin filaments and microtubules, which positions them as important regulators of cytoarchitecture. Septin 9 (Sept9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short MAP-like motif unique to Sept9 isoform 1 (Sept9_i1) drives septin octamer-microtubule interaction in cells andin vitroreconstitutions. Septin-microtubule association requires polymerizable septin octamers harboring Sept9_i1. Although outside of the MAP-like motif, HNA mutations abrogates this association, identifying a putative regulatory domain. Removal of this domain from Sept9_i1 sequesters septins on microtubules, promotes microtubule stability and alters actomyosin fiber distribution and tension. Thus, we identify key molecular determinants and potential regulatory roles of septin-microtubule interaction, paving the way to deciphering the mechanisms underlying septin associated pathologies.
Explainable Feature Extraction Using a Neural Network with non-Synaptic Memory for Hand-Written Digit Classification
Authors: Faghihi Faramarz , Alashwal Hany , Moustafa Ahmed A. 
Published: April 2021

AbstractThe human brain recognizes hand-written digits by extracting the features from a few training samples that compose the digit image including horizontal, vertical, and orthogonal lines as well as full or semi-circles. In this study, we present a novel brain-inspired method to extract such features from handwritten digits images in the MNIST database (Modified National Institute of Standards and Technology database). In this study, we developed an explainable feature extraction method for hand written digit classification in which the extracted information are stored inside the neurons as non-synaptic memory manner. For this purpose, a neural network with 10 single neurons was trained to extract features of training images (each neuron represents one digit class). Following that, the trained single neurons are used for the retrieval of information from test images in order to assign them to digit categories. The accuracy of the classification method of test set images is calculated for different number of training samples per digit. The method demonstrates 75 % accuracy using 0.016 % of the training data and maximally shows accuracy 86 % using one epoch of whole training data. The method as an understandable feature extraction method allows users to see how it works and why it does not perform well on some digit classes. To our knowledge, this is the first model that stores information inside single neurons (i.e., non-synaptic memory) instead of storing the information in synapses of connected layers. Due to enabling single neurons to compute individually, it is expected that such class of neural networks show higher performance compared to traditional neural networks used in complicated classification problems.
Rose Extract Treatment on the CD4+ T lymphocytes
Authors: Arokiaraj Mark Christopher , Menesson Eric 
Published: April 2021

AbstractBackground and AimsTo study the effect of rose extract on CD4+T lymphocytes, and assess the cytokines response after cell treatment. In our previous study on endothelial cells, the rose extract reduced the secretion of inflammatory markers significantly.MethodsThe red rose extract used in this study was prepared and stored until use at -20°C. T cells were seeded in 96-well plates at 313500 cells/well in 100μl of cell culture medium in duplicate, one half of the wells were used for biomarkers screening in the culture medium, and the other half for cytotoxicity assay. 24h after plating, the cells were treated in duplicate with 100μl of red rose extract diluted at 0.5%, 0.1%, 0.05%, 0.01% and 0.005% (v/v) in cell culture medium or with culture medium only as control for 72h. Some other wells were for untreated cells, and cells treated with rose extract at 0.005% for 48h incubation time. After 48h and 72h, the corresponding wells were used for the cytotoxicity assay and from the duplicate wells, the cell culture media were collected and stored at -80°C until the biomarkers screening assay.ResultsCytotoxicity assay revealed insignificant changes. IFN-gamma, MCP-1, GRO, RANTES and TIMP, Angiopoietin 1 and MMP-9 were elevated. Except MMP-9 which had fold changes >2 other cytokines were minimally elevated at various concentrations and timing of rose extract treatment. None of the cytokines were less than 0.8-fold.ConclusionsUnlike in the endothelial cells, there is mild elevation in few inflammatory markers on T lymphocytes treatment by rose extract. Further studies need to be performed to estimate the clinical relevance.
On the Analysis of Transcriptional Noise From RNA-sequencing Data
Authors: Vitting-Seerup Kristoffer 
Published: April 2021

AbstractRNA-sequencing (RNA-seq) has revolutionized our understanding of molecular and cellular biology. A central cornerstone in the analysis of RNA-seq is the bioinformatic tools that quantify the data. To evaluate the efficacy of these tools, scientists rely heavily on simulation of RNA-seq. Recently Varabyouet al. took simulation of RNA-seq data to the next level by providing simulated data, that includes simulation of transcriptional noise. While this represents a significant step forward in our ability to perform realistic benchmarks of RNA-seq tools, the data provided by Varabyouet al. need refinement. In the following, I suggest a few improvements with a specific focus on splicing noise.PrefaceI wrote this paper intending to submit it as a Commentary on the Varabyouet al. 2020 Genome Research paper1, but apparently, Genome Research does not publish correspondence-type articles. That is why it is currently on BioRxiv. If you have suggestions about where this paper could potentially be published do not hesitate to contact me.
De novomutations in domestic cat are consistent with an effect of reproductive longevity on both the rate and spectrum of mutations
Authors: Wang Richard J. , Raveendran Muthuswamy , Alan Harris R. , Murphy William J. , Lyons Leslie A. , Rogers Jeffrey , Hahn Matthew W. 
Published: April 2021

AbstractThe mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health and function of individuals. Here, we examine this important parameter in the domestic cat, a beloved companion animal as well as a valuable biomedical model. We estimate a mutation rate of 0.86 × 10-8per bp per generation for the domestic cat (at an average parental age of 3.8 years). We find evidence for a significant paternal age effect, with more mutations transmitted by older sires. Our analyses suggest that the cat and the human have accrued similar numbers of mutations in the germline before reaching sexual maturity. The per-generation mutation rate in the cat is 28% lower than what has been observed in humans, but is consistent with the shorter generation time in the cat. Using a model of reproductive longevity, which takes into account differences in the reproductive age and time to sexual maturity, we are able to explain much of the difference in per-generation rates between species. We further apply our reproductive longevity model in a novel analysis of mutation spectra and find that the spectrum for the cat resembles the human mutation spectrum at a younger age of reproduction. Together, these results implicate changes in life-history as a driver of mutation rate evolution between species. As the first direct observation of the paternal age effect outside of rodents and primates, our results also suggest a phenomenon that may be universal among mammals.
Preliminaryin silicoexperiments: Towards new cancer treatments?
Authors: Fliess Michel , Join Cédric , Moussa Kaouther , Djouadi Seddik M. , Alsager Mohamed 
Published: April 2021

AbstractWe present some “in silico” experiments to design combined chemo- and immunotherapy treatment schedules. We introduce a new framework by combining flatness-based control along with model-free control. The flatness property of the used mathematical model yields straightforward reference trajectories. They provide us with the nominal open-loop control inputs. Closing the loop via model-free control allows to deal with the uncertainties on the injected drug doses. Several numerical simulations illustrating different case studies are displayed. We show in particular that the considered health indicators are driven to the safe region, even for critical initial conditions. Furthermore, in some specific cases there is no need to inject chemotherapeutic agents.
Maize RAMOSA3 accumulates in nuclear condensates enriched in RNA POLYMERASE II isoforms during the establishment of axillary meristem determinacy
Authors: Demesa-Arevalo Edgar , Abraham-Juarez Maria Jazmin , Xu Xiaosa , Bartlett Madelaine , Jackson David 
Published: April 2021

Brief AbstractMaize meristem determinacy is regulated by Trehalose-6-Phosphate Phosphatase (TPP) metabolic enzymes RAMOSA3 and TPP4. However, this function is independent of their enzymatic activity, suggesting they have an unpredicted, or moonlighting function. Using whole-mount double immunolabeling and imaging processing, we investigated the co-localization of RA3 nuclear speckles with markers for transcription, chromatin state and splicing. We find evidence for RA3 co-localization with RNA POL II, a transcription marker, and not with markers for promoter chromatin remodeling or mRNA processing, suggesting a function of nuclear RA3 in mediating a transcriptional response during meristem determinacy.
Precise gene models using long-read sequencing reveal a unique poly(A) signal inGiardia lamblia
Authors: Bilodeau Danielle Y. , Sheridan Ryan M. , Balan Balu , Jex Aaron R. , Rissland Olivia S. 
Published: April 2021

ABSTRACTDuring pre-mRNA processing, the poly(A) signal is recognized by a protein complex that ensures precise cleavage and polyadenylation of the nascent transcript. The location of this cleavage event establishes the length and sequence of the 3′ UTR of an mRNA, thus determining much of its post-transcriptional fate. Here, using long-read sequencing, we characterize the polyadenylation signal and related sequences surroundingGiardia lambliacleavage sites for over 2600 genes. We find thatG. lambliauses a AGURAA poly(A) signal, which differs from the mammalian AAUAAA. We also describe howG. lamblialacks common auxiliary elements found in other eukaryotes, along with the proteins that recognize them. Further, we identify 133 genes that show evidence of alternative polyadenylation. These results suggest that despite pared down cleavage and polyadenylation machinery, 3′ end formation still appears to be an important regulatory step for gene expression inG. lamblia.
Integrative multi-omics analysis reveals conserved hierarchical mechanisms of FOXO3 pioneer-factor activity
Authors: Brown Abigail K. , Maybury-Lewis Sun Y. , Webb Ashley E. 
Published: April 2021

AbstractFOXO transcription factors are critical for cellular homeostasis and have been implicated in longevity in several species. Yet how these factors directly affect aging, particularly in humans, is not well understood. Here, we take an integrated multi-omics approach to identify the chromatin-level mechanisms by which FOXO3 coordinates transcriptional programs. We find that FOXO3 functions as a pioneer factor in human cells, directly altering chromatin accessibility to regulate gene expression. Unexpectedly, FOXO3’s pioneer activity at many sites is achieved through a two-step process, in which chromatin accessibility is initially reduced, then transitions to an open conformation. The direct FOXO3 network comprises chromatin remodelers, including the SWI/SNF remodeling complex, which we find is functionally required for FOXO3 activity. We also identify a novel secondary network of activator protein-1 (AP-1) transcription factors deployed by FOXO3, which orchestrate a neuronal-specific subnetwork. Together, this hierarchical FOXO3 pioneer network regulates key cellular processes including metabolism, proteostasis, epigenetics and proliferation, which must be tightly controlled under changing conditions that accompany aging.
Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla
Authors: Follansbee Taylor , Domocos Dan , Nguyen Eileen , Nguyen Amanda , Bountouvas Aristea , Velasquez Lauren , Carstens Mirela Iodi , Takanami Keiko , Ross Sarah E. , Carstens E. 
Published: April 2021

AbstractThe rostral ventromedial medulla (RVM) is important in descending modulation of spinal nociceptive transmission, but it is unclear if the RVM also modulates spinal pruriceptive transmission. RVM ON cells are activated by noxious algesic and pruritic stimuli and are pronociceptive. Many RVM-spinal projection neurons express the neurokinin-1 receptor (Tacr1), and ON-cells are excited by local administration of substance P (SP). We hypothesized that Tacr1-expressing RVM ON cells exert an inhibitory effect on itch opposite to their pronociceptive action. Intramedullary microinjection of SP significantly potentiated RVM ON cells and reduced pruritogen-evoked scratching while producing mild mechanical sensitization. Chemogenetic activation of RVM Tacr1-expressing RVM neurons also reduced acute pruritogen-evoked scratching. Optotagging experiments confirmed RVM Tacr1-expressing neurons to be ON cells. We conclude that Tacr1-expressing ON cells in RVM play a significant role in the modulation of pruriceptive transmission.