bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generating dynamic carbon-dioxide from the respiratory-volume time series: A feasibility study using neural networks
Authors: Agrawal V. , Zhong Xiaole Z. , Chen J. J. 
Published: July 2022

AbstractIn the context of fMRI, carbon dioxide (CO2) is a well-known vasodilator that has been widely used to monitor and interrogate vascular physiology. Moreover, spontaneous fluctuations in end-tidal carbon dioxide (PETCO2) reflects changes in arterial CO2 and has been demonstrated as the largest physiological noise source in the low-frequency range of the resting-state fMRI (rs-fMRI) signal. Increasing appreciation for the role of CO2 in fMRI has given rise to methods that use it for physiological denoising or estimating cerebrovascular reactivity. However, the majority of rs-fMRI studies do not involve CO2 recordings, and most often only heart rate and respiration are recorded. While the intrinsic link between these latter metrics and CO2 led to suggested possible analytical models, they have not been widely applied. In this proof-of-concept study, we propose a deep learning approach to reconstruct CO2 and PETCO2 data from respiration waveforms in the resting state. We demonstrate that the one-to-one mapping between respiration and CO2 recordings can be well predicted using fully convolutional networks (FCNs), achieving a Pearson correlation coefficient (r) of 0.946 ± 0.056 with the ground truth CO2. Moreover, dynamic PETCO2 can be successfully derived from the predicted CO2, achieving r of 0.512 ± 0.269 with the ground truth. Importantly, the FCN-based methods outperform previously proposed analytical methods. In addition, we provide guidelines for quality assurance of respiration recordings for the purposes of CO2 prediction. Our results demonstrate that dynamic CO2 can be obtained from respiration-volume using neural networks, complementing the still few reports in deep-learning of physiological fMRI signals, and paving the way for further research in deep-learning based bio-signal processing.
MINE is a method for detecting spatial density of regulatory chromatin interactions based on a MultI-modal NEtwork
Authors: Gong Haiyan , Li Minghong , Ji Mengdie , Zhang Xiaotong , Yuan Zan , Zhang Sichen , Yang Yi , Li Chun , Chen Yang 
Published: July 2022

SUMMARYChromatin interactions play essential roles in chromatin conformation and gene expression. However, few tools exist to analyze the spatial density of regulatory chromatin interactions. Here, we present the MultI-modal NEtwork (MINE) toolkit, including MINE-Loop, MINE-Density, and MINE-Viewer. MINE-Loop network modeling integrates Hi-C, ATAC-seq, and histone ChIP-seq data to enhance the detection of regulatory chromatin interactions (RCIs, i.e., chromatin interactions that are anchoring regulatory elements to chromatin); MINE-Density quantifies the spatial density of regulatory chromatin interactions identified by MINE-Loop within different chromatin conformations; and MINE-Viewer facilitates 3D visualization of the density of chromatin interactions and participating regulatory factors, such as transcription factors. We applied MINE to investigate the relationship between the spatial density of regulatory chromatin interactions (SD-RCI) and chromatin volume change in HeLa cells before and after liquid-liquid phase separation. Changes in SD-RCI before and after treating the HeLa cells with 1,6-hexanediol showed that the change in chromatin volume was related to the degree of activation or repression of genes in chromatin interactions. The MINE toolkit provides a new method for quantitative study of chromatin conformation.Graphical AbstractIn BriefGong et al. provide a toolkit MINE to explore the relationship between spatial density of regulatory chromatin interactions, gene expression and chromatin structure change.HighlightsMINE toolkit was provided to detect more regulatory chromatin interactions (RCI), count the spatial density of regulatory chromatin interactions and visualize the density of chromatin interactions with transcription factors in three-dimension.Chromatin regions were divided into developed active hub, developing active hub, developed repressive hub, and developing repressive hub according to the density of active or repressive regulatory chromatin interactions.The change of chromatin structure before and after liquid-liquid phase separation is quantitively described by using the MINE toolkit.
Correction of susceptibility distortion in EPI: a semi-supervised approach with deep learning
Authors: Legouhy Antoine , Graham Mark , Guerreri Michele , Stee Whitney , Villemonteix Thomas , Peigneux Philippe , Zhang Hui 
Published: July 2022

AbstractEcho planar imaging (EPI) is the most common approach for acquiring diffusion and functional MRI data due to its high temporal resolution. However, this comes at the cost of higher sensitivity to susceptibility-induced B0 field inhomogeneities around air/tissue inter-faces. This leads to severe geometric distortions along the phase encoding direction (PED). To correct this distortion, the standard approach involves an analogous acquisition using an opposite PED leading to images with inverted distortions and then non-linear image registration, with a transformation model constrained along the PED, to estimate the voxelwise shift that undistorts the image pair and generates a distortion-free image. With conventional image registration approaches, this type of processing is computationally intensive. Recent advances in unsupervised deep learning-based approaches to image registration have been proposed to drastically reduce the computational cost of this task. However, they rely on maximizing an intensity-based similarity measure, known to be suboptimal surrogate measures of image alignment. To address this limitation, we propose a semi-supervised deep learning algorithm that directly leverages ground truth spatial transformations during training. Simulated and real data experiments demonstrate improvement to distortion field recovery compared to the unsupervised approach, improvement image similarity compared to supervised approach and precision similar to TOPUP but with much faster processing.
Evolutionary stability of social commitment
Authors: Shirokawa Yuka , Shimada Masakazu , Shimada Nao , Sawai Satoshi 
Published: July 2022

AbstractConflict resolution between individual cells and a group is essential for multicellularity. The social amoebaDictyostelium discoideumswitches between solitary growth and social fruitification depending on nutrient availability. Under starvation, cells form fruiting bodies consisting of spores and non-viable altruistic stalk cells. Once cells socially committed, they complete fruitification even with a renewed source of nutrients. This social commitment is puzzling because it deprives individual cells of benefits of quickly resuming solitary growth. One idea posits that traits that facilitate premature de-commitment are somehow hindered from being selected. We studied outcomes of premature de-commitment by forced refeeding. We show that when refed cells resume sociality together with non-refed cells, besides some becoming solitary outside of fruiting bodies, a large fraction was redirected to a sub-region of altruistic stalk regardless of their original fate. The refed cells exhibited reduced cohesivity and were sorted out to the altruistic positions in morphogenesis. Furthermore, a theoretical model considering evolution of cell-cell association revealed a valley in the fitness landscape that prevents invasion of de-committing mutants. Our results provide a general scheme that naturally penalizes withdrawal from a society by evolving a specific division of labor that less cohesive individuals become altruists.Significance StatementEvolution of unicellular to multicellular organisms must resolve conflicts of reproductive interests between individual cells and the group. In the social amoebaDictyostelium, a transition from a solitary to multicellular group occurs under starvation. Once cells commit themselves to multicellular organization, the process continues even when shifting to an environment that favors solitary growth. Our study revealed that cells forced to partially revert to a de-committed state take an altruistic role through interaction with socially committed cells. The de-committed cells exhibited reduced cohesivity and were sorted out to altruistic positions in morphogenesis. This inevitably penalizes ‘selfish’ cells that revert to solitary growth too quickly. Our results explain group-level behavior that is apparently difficult to understand from an individual-level fitness.
AlphaViz: Visualization and validation of critical proteomics data directly at the raw data level
Authors: Voytik Eugenia , Skowronek Patricia , Zeng Wen-Feng , Tanzer Maria C. , Brunner Andreas-David , Thielert Marvin , Strauss Maximilian T. , Willems Sander , Mann Matthias 
Published: July 2022

ABSTRACTAlthough current mass spectrometry (MS)-based proteomics identifies and quantifies thousands of proteins and (modified) peptides, only a minority of them are subjected to in-depth downstream analysis. With the advent of automated processing workflows, biologically or clinically important results within a study are rarely validated by visualization of the underlying raw information. Current tools are often not integrated into the overall analysis nor readily extendable with new approaches. To remedy this, we developed AlphaViz, an open-source Python package to superimpose output from common analysis workflows on the raw data for easy visualization and validation of protein and peptide identifications. AlphaViz takes advantage of recent breakthroughs in the deep learning-assisted prediction of experimental peptide properties to allow manual assessment of the expected versus measured peptide result. We focused on the visualization of the 4-dimensional data cuboid provided by Bruker TimsTOF instruments, where the ion mobility dimension, besides intensity and retention time, can be predicted and used for verification. We illustrate how AlphaViz can quickly validate or invalidate peptide identifications regardless of the score given to them by automated workflows. Furthermore, we provide a ‘predict mode’ that can locate peptides present in the raw data but not reported by the search engine. This is illustrated the recovery of missing values from experimental replicates. Applied to phosphoproteomics, we show how key signaling nodes can be validated to enhance confidence for downstream interpretation or follow-up experiments. AlphaViz follows standards for open-source software development and features an easy-to-install graphical user interface for end-users and a modular Python package for bioinformaticians. Validation of critical proteomics results should now become a standard feature in MS-based proteomics.
A Comparative Study of Epithelial Transport in the Rat and Mouse Kidneys: Modelling and Analysis
Authors: Layton Anita T. 
Published: July 2022

AbstractThe goal of the present study was to investigate the functional implications of sex and species differences in the pattern of transporters along nephrons in the rat and mouse kidney, as reported by Veiras et al. (J Am Soc Nephrol28: 3504–3517, 2017). To do so, we developed the first sex-specific computational models of epithelial water and solute transport along the nephrons from male and female mouse kidneys, and conducted simulations along with our published rat models. These models account for the sex differences in the abundance of apical and basolateral transporters, glomerular filtration rate, and tubular dimensions. Model simulations predict that 73% and 57% of filtered Na+is reabsorbed by the proximal tubules of male and female rat kidneys, respectively. Due to their smaller transport area and lower NHE3 activity, the proximal tubules in the mouse kidney reabsorb a significantly smaller fraction of the filtered Na+, at 53% in male and only 34% in female. The lower proximal fractional Na+reabsorption in female kidneys of both rat and mouse is due primarily to their smaller transport area, lower Na+/H+exchanger activity, and lower claudin-2 abundance, culminating in significantly larger fractional delivery of water and Na+to the downstream nephron segments in female kidneys. Conversely, the female distal nephron exhibits a higher abundance of key Na+transporters, including Na+-Cl−cotransporters in both species, epithelial Na+channels for the female rat, and Na+-K+-Cl−cotransporters for the female mouse. The higher abundance of transporters accounts for the enhanced water and Na+transport along the female rat and mouse distal nephrons, relative to the respective male, resulting in similar urine excretion between the sexes. Model simulations indicate that the sex and species differences in renal transporter patterns may partially explain the experimental observation that, in response to a saline load, the diuretic and natriuretic responses were more rapid in female rats than males, but no significant sex difference was found in mice. These computational models can serve as a valuable tool for analyzing findings from experimental studies conducted in rats and mice, especially those involving genetic modifications.
A pH-dependent cluster of charges in a conserved cryptic pocket on flaviviral envelopes
Authors: Zuzic Lorena , Marzinek Jan K. , Anand Ganesh S. , Warwicker Jim , Bond Peter J. 
Published: July 2022

ABSTRACTFlaviviruses are enveloped viruses which include numerous human pathogens of escalating global health concern that are predominantly transmitted by mosquitoes and ticks. Some, such as dengue virus, exhibit the phenomenon of antibody-dependent enhancement (ADE) of disease, making traditional vaccine-based routes of fighting viral infections problematic. The pH-dependent conformational change of the envelope (E) protein required for fusion between the viral and endosomal membranes is an attractive point of inhibition by antivirals as it also has the potential to diminish the effects of ADE. Here, we systematically examined six flaviviruses by employing large-scale molecular dynamics (MD) simulations of a ∼400,000 atom raft system that represents a substantial portion of the curved flaviviral envelope. We utilised a benzene-mapping approach over a total of 14 μs of sampling time, leading to discovery of shared hotspots and elucidation of the dynamic behaviour of conserved cryptic sites. A cryptic pocket previously shown to bind a detergent molecule exhibited significant strain-specific characteristics. An alternative conserved cryptic site located at the E protein domain interfaces showed a more consistent dynamic behaviour across flaviviruses and contains a buried, conserved cluster of ionisable residues that includes His144, previously implicated in the pH-dependent conformational switch required for fusion. The dynamics of the cluster were further explored in extensive constant-pH simulations and revealed cluster and domain-interface disruption under low pH conditions. Based on this, we propose a cluster-dependent mechanism that addresses inconsistencies in the histidine-switch hypothesis and highlights the role of cluster protonation in orchestrating the domain dissociation pivotal for the formation of the fusogenic trimer.GRAPHICAL ABSTRACT
Shared and host-specific transcriptomic response of Pseudomonas donghuensis P482 to the exudates of tomato (Dicot) and maize (Monocot) shed light on the host-adaptive traits in the promiscuous root colonizing bacteria
Authors: Krzyżanowska Dorota M. , Jabłońska Magdalena , Kaczyński Zbigniew , Czerwicka-Pach Małgorzata , Macur Katarzyna , Jafra Sylwia 
Published: July 2022

AbstractPlants of different genotypes and physiological states recruit different populations of root microbiota. The selection is driven by the immune response of the plant and the composition of root exudates. Some bacteria, including Pseudomonas spp., are promiscuous root colonizers. It is yet unclear what particular changes in lifestyle enable them to thrive in the company of different plant hosts. In this study, we used RNAseq to identify genes of the differential (host-specific) and shared (host-independent) transcriptomic responses of a biocontrol strain Pseudomonas donghuensis P482 to the root exudates of two phylogenetically distinct plant species, tomato (Dicot) and maize (Monocot), both of which can be colonized by the bacterium. The host-independent response of P482 to exudates involved upregulated expression of arsenic resistance genes and bacterioferritin synthesis. Contrary, we observed downregulation of pathways related to sulfur assimilation, sensing of ferric citrate and/or other iron carriers, the acquisition of heme, the assembly of the type VI secretion system, and amino acid transport. Pathways upregulated in P482 specifically by tomato exudates included nitric oxide detoxification, repair of iron-sulfur clusters, respiration through the cyanide-insensitive cytochrome bd, and catabolism of amino acids and/or fatty acids. The maize-specific response included upregulation of genes associated with motility, the activity of MexE and two other RND efflux pumps, and copper tolerance. To provide more context to the study, we determined the chemical composition of exudates by GC-MS, NMR, and LC-SRM. Our results bring new insight into the host-driven metabolic adaptations of promiscuous root colonizing bacteria.Significance statementUnderstanding factors determining the composition and the activity of plant-associated microbiota is crucial to harnessing their potential to benefit plant health. Traits that enable microorganisms to colonize plants have long been the subject of study, with many important factors identified for particular host-microbe systems. However, studies involving more than a single plant host are rare. This results in many unanswered questions on the host-specific and universal aspects of metabolism that enable more promiscuous root colonizers to interact with different plant hosts. The presented study begins to fill this knowledge gap by providing data on the metabolic pathways involved in the differential and shared response of Pseudomonas donghuensis strain P482 to the exudates of phylogenetically distant plant species: tomato and maize.
Comparing the accuracy and efficiency of third generation DNA barcode sequencing: Oxford Nanopore Technologies versus Pacific Biosciences
Authors: Cuber Piotr , Chooneea Darren , Geeves Clementine , Salatino Silvia , Creedy Thomas J. , Griffin Claire , Sivess Laura , Barnes Ian , Price Ben , Misra Raju 
Published: July 2022

ABSTRACTAt times of drastic decrease in biodiversity and loss of species, sometimes referred to as the “sixth mass extinction” or “Holocene extinction”, there is a high demand on the development of effective tools for studying and monitoring biodiversity. In the past decade, new promising technologies, such as third generation sequencing (TGS), enabled massive, rapid, and cost-effective data analysis of non-model organisms, accelerating taxonomic identification studies and contributing to conservation applications. Here, we focus on the comparison of the two main TGS providers, Pacific Biosciences (PacBio), and Oxford Nanopore Technologies (ONT), for the purpose of DNA barcoding. For ONT, we also tested selected combinations of different types of flow cells and ligation sequencing kits. Out of five tested combinations (PacBio, ONT Flongle flow cell & SQK-LSK110 kit, R9 flow cell & SQK-LSK109 kit, R9 & SQK-LSK100 kit, and R10 flow cell & Q20+ chemistry kit), ONT’s Flongle turned out to be most variable in returning the results, but at the same time the most cost efficient. The highest numbers of successfully sequenced samples were achieved with the ONT’s R10 & Q20+ chemistry combination. In terms of library preparation time, ONT protocols are the quickest, whereas regarding cost effectiveness - using Sanger pricing per sample as a cut-off - various technologies become affordable depending on the number of samples used. Although both tested platforms are suitable for DNA barcoding, we further discuss their limitations and applicability to different studies, with a special focus on the price and the number of samples. The pipeline we developed, from whole specimens to final DNA barcode consensuses, can aid planning and budgeting biodiversity studies, maximising the number of specimens sequenced in one run and speeding up the sample processing time.
Structural and functional landscape of α-synuclein fibril conformations amplified from cerebrospinal fluid
Authors: Sokratian Arpine , Zhou Ye , Xu Enquan , Viverette Elizabeth , Dillard Lucas , Yuan Yuan , Li Joshua Y. , Matarangas Ariana , Bouvette Jonathan , Borgnia Mario , Bartesaghi Alberto , West Andrew 
Published: July 2022

AbstractLewy body dementias are pathologically defined by the deposition of α-synuclein fibrils into inclusions throughout the brain. Cerebrospinal fluid(CSF) in disease harbors circulating α-synuclein-fibril seeds, and parental α-synuclein fibrils can template core structure into amplified fibrils. Using cryo-electron microscopy, we identify six novel α-synuclein fibril assemblies amplified from ten CSF samples (3.8Å to 2.9Å nominal resolutions). Fibrils are classified based on two types of filament interaction, two types of β-sheet stacking, and two types of hydrophobic pocket. CSF-amplified fibril products have one, two, or three distinct assemblies each. Six of ten samples share a common fibril assembly. Within this classification, the fibrils have distinct profiles in amyloid dye binding, and dramatically different potencies in both seeding new inclusions in neurons and evoked microglial pro-inflammatory responses. However, no single structural feature predicts functional phenotypes. Our results highlight CSF as a valuable resource to identify novel α-synuclein assemblies potentially important in disease.
Genetic and geometric heredity interact to drive polarized flow in the Drosophila embryo
Authors: Gehrels Emily , Chakrabortty Bandan , Merkel Matthias , Lecuit Thomas 
Published: July 2022

AbstractTissue flow during morphogenesis is commonly driven by local constriction of cell cortices, which is caused by activation of actomyosin contractility. This can lead to long-range flows due to tissue viscosity. However, in the absence of cell-intrinsic polarized forces or polarity in forces external to the tissue, these flows must be symmetric and centered around the region of contraction. Polarized tissue flows have been previously demonstrated to arise from the coupling of such contractile flows to points of increased friction or adhesion to external structures. However, we show with experiments and modeling that the onset of polarized tissue flow in early Drosophila morphogenesis occurs independent of adhesion and is instead driven by a geometric coupling of apical actomyosin contractility to tissue curvature. Particularly, the onset of polarized flow is driven by a mismatch between the position of apical myosin activation and the position of peak curvature at the posterior pole of the embryo. Our work demonstrates how genetic and geometric information inherited from the mother interact to create polarized flow during embryo morphogenesis.