bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the efficacy of data-driven denoising methods for a multi-echo fMRI acquisition at 7T
Authors: Beckers Abraham B. , Poser Benedikt A. , Keszthelyi Daniel 
Published: July 2022

AbstractIn functional magnetic resonance imaging (fMRI) of the brain the signal is dominated by (physiological) noise. Imaging at ultrahigh field strength is becoming increasingly popular as it offers increased spatial accuracy. The latter is of particular benefit in brainstem neuroimaging given the small cross-sectional area of most nuclei. Physiological noise scales with field strength in fMRI acquisitions, however. Although this problem is in part solved by decreasing voxel size, it is clear that adequate physiological denoising is of utmost importance in brainstem-focused fMRI experiments. Multi-echo sequences have been reported to facilitate highly effective denoising through TE-dependence of Blood Oxygen Level Dependent (BOLD) signals, in a denoising method referred to as multi-echo independent component analysis (ME-ICA). It has not been explored previously how ME-ICA compares to other data-driven denoising approaches at ultrahigh field strength. In the current study, we compared the efficacy of several denoising methods, including anatomical component based correction (aCompCor), Automatic Removal of Motion Artifacts (ICA-AROMA), ME-ICA, and a combination of ME-ICA and aCompCor. We assessed several data quality metrics, including temporal signal-to-noise ratio (tSNR), delta variation signal (DVARS) and spectral density of the global signal. Moreover, we looked at the ability of each method to uncouple the global signal and respiration. In line with previous reports at lower field strengths, we demonstrate that after applying ME-ICA, the data is best post-processed in order to remove spatially diffuse noise with a method such as aCompCor. Our findings indicate that ME-ICA combined with aCompCor and ICA-AROMA are highly effective denoising approaches for multi-echo data acquired at 7T. ME-ICA combined with aCompCor potentially preserves more signal-of-interest as compared to ICA-AROMA.Highlights-ME-ICA and ICA-AROMA provide effective denoising for multi-echo 7T fMRI data-High tSNR can be achieved in the brainstem with a multi-echo acquisition at 7T-After ME-ICA, the data is best post-processed to correct for spatially diffuse noise
Genomic heterogeneity in pancreatic cancer organoids and its stability with culture
Authors: Usman Olalekan , Zhang Liting , Xie Gengqiang , Kocher Hemant M , Hwang Chang-il , Wang Yue Julia , Mallory Xian Fan , Irianto Jerome 
Published: July 2022

AbstractThe establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. Among the outstanding questions in pancreatic cancer biology are the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoids, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the functionality of these copy number alterations.
UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells
Authors: Chen Chengyan , Shen Yanmin , Li Luqian , Ren Yaoxin , Wang Zhao-Qi , Li Tangliang 
Published: July 2022

AbstractNonsense-mediated mRNA decay (NMD) is a highly conserved regulatory mechanism of post-transcriptional gene expression in eukaryotic cells. NMD plays essential roles in mRNA quality and quantity control, and thus safeguards multiple biological processes including embryonic stem cell differentiation and organogenesis. UPF3A and UPF3B in vertebrate species, originated from a singleUPF3gene in yeast, are key factors in the NMD machinery. While UPF3B is a well-recognized weak NMD-promoting factor, whether UPF3A functions in promoting or suppressing NMD is under debate. In this study, we generated aUpf3aconditional knockout mouse strain, and established multiple lines of embryonic stem cells and somatic cells without UPF3A. Through extensive analysis on the expressions of 33 NMD targets, we found UPF3A neither represses NMD in mouse embryonic stem cells, somatic cells, nor in major organs including the liver, spleen, and thymus. Our study reinforces that UPF3A is dispensable for NMD when UPF3B is present. Furthermore, UPF3A may weakly and selectively promote NMD in certain murine organs.Summary blurbWe generated a newUpf3ainducible knockout mouse model and showed that UPF3A does not repress expressions of NMD target genes in embryonic stem cells, somatic fibroblasts, as well as multiple tissues from adult mice.
Excessive fluid shear stress-mediated Klf4 leads to arteriovenous pathogenesis
Authors: Banerjee Kuheli , Lin Yanzhu , Gahn Johannes , Gupta Purnima , Graupera Mariona , Dobreva Gergana , Schwartz Martin , Ola Roxana 
Published: July 2022

AbstractBackgroundVascular networks form, remodel and mature under the influence of both fluid shear stress (FSS) and soluble factors. For example, FSS synergizes with Bone Morphogenic Protein 9 (BMP9) and BMP10 to promote and maintain vascular stability. Mutation of the BMP receptors ALK1, Endoglin or the downstream effector SMAD4 leads to Hereditary Hemorrhagic Telangiectasia (HHT), characterized by fragile and leaky arterial-venous malformations (AVMs). But how endothelial cells (EC) integrate FSS and BMP signals in normal vascular development and homeostasis, and how mutations give rise to malformations is not well understood.ResultsHere we show that loss of Smad4 in murine ECs increases cells’ sensitivity to flow and the resulting AVMs are characterized by excessive elongation and polarity against the flow. Smad4 deletion also blocks the anti-proliferative response to high FSS, leading to loss of arterial identity. Our data show that loss of cell cycle arrest leads to loss of arterial identity, which is essential in AVM formation upon Smad4 depletion in ECs. Excessive flow-induced activation of KLF4-PI3K/AKT due to Cyclin dependent Kinase (CDK) activation mediates the aberrant morphological responses to flow triggering AVM formation.ConclusionsOur results show that loss of polarization against the flow is not required for AVM formation upon EC Smad4 depletion. Instead, increased EC proliferation-mediated loss of arterial identity due to flow-induced PI3K/Akt/Cdks hyperactivation and Klf4 over-expression are the main events associated with AVM formation.
Dissecting peripheral protein-membrane interfaces
Authors: Tubiana Thibault , Sillitoe Ian , Orengo Christine , Reuter Nathalie 
Published: July 2022

ABSTRACTPeripheral membrane proteins (PMPs) include a wide variety of proteins that have in common to bind transiently to the chemically complex interfacial region of membranes through their interfacial binding site (IBS). In contrast to protein-protein or protein-DNA/RNA interfaces, peripheral protein-membrane interfaces are poorly characterized.We collected a dataset of PMP domains representative of the variety of PMP functions: membrane-targeting domains (Annexin, C1, C2, discoidin C2, PH, PX), enzymes (PLA, PLC/D) and lipid-transfer proteins (START). The dataset contains 1328 experimental structures and 1194 AphaFold models. We mapped the amino acid composition and structural patterns of the IBS of each protein in this dataset, and evaluated which were more likely to be found at the IBS compared to the rest of the domains’ accessible surface.In agreement with earlier work we find that about two thirds of the PMPs in the dataset have protruding hydrophobes (Leu, Ile, Phe, Tyr, Trp and Met) at their IBS. The three aromatic amino acids Trp, Tyr and Phe are a hallmark of PMPs IBS regardless of whether they protrude on loops or not. This is also the case for lysines but not arginines suggesting that, unlike for Arg-rich membrane-active peptides, the less membrane-disruptive lysine is preferred in PMPs. Another striking observation was the over-representation of glycines at the IBS of PMPs compared to the rest of their surface, possibly procuring IBS loops a much-needed flexibility to insert in-between membrane lipids. The analysis of the 9 superfamilies revealed amino acid distribution patterns in agreement with their known functions and membrane-binding mechanisms. Besides revealing novel amino acids patterns at protein-membrane interfaces, our work contributes a new PMP dataset and an analysis pipeline that can be further built upon for future studies of PMPs properties, or for developing PMPs prediction tools using for example, machine learning approaches.
A parasitic fungus employs mutated eIF4A to survive on rocaglate-synthesizing Aglaia plants
Authors: Chen Mingming , Kumakura Naoyoshi , Muller Ryan , Shichino Yuichi , Nishimoto Madoka , Mito Mari , Gan Pamela , Ingolia Nicholas T. , Shirasu Ken , Ito Takuhiro , Iwasaki Shintaro 
Published: July 2022

SummaryPlants often generate secondary metabolites as defense mechanisms against parasites. Although some fungi may potentially overcome the barrier of antimicrobial compounds, only a limited number of examples and molecular mechanisms of resistance have been reported. Here, we found an Aglaia plant-parasitizing fungus that overcomes the toxicity of rocalgates, which are translation inhibitors synthesized by the plant, through an amino acid substitution in a translation initiation factor (eIF). De novo transcriptome assembly revealed that the fungus belongs to Ophiocordyceps genus and its eIF4A, a molecular target of rocaglates, contains a amino acid substitution critical for rocaglate binding. Ribosome profiling harnessing a cucumber-infecting fungus, Colletotrichum orbiculare, demonstrated that the translational inhibitory effects of rocaglates were largely attenuated by the mutation found in the Aglaia parasite. The engineered Colletotrichum orbiculare showed a survival advantage on cucumber plants with rocaglates. Our study exemplifies a plant-fungus tug-of-war centered on secondary metabolites produced by host plants.
Odd skipped-related 1 controls the pro-regenerative response of Fibro-Adipogenic Progenitors
Authors: Kotsaris Georgios , Qazi Taimoor H. , Bucher Christian H. , Pöhle-Kronawitter Sophie , Ugorets Vladimir , Jarassier William , Börno Stefan , Timmermann Bernd , Giesecke-Thiel Claudia , Vallecillo-García Pedro , Economides Aris N. , Grand Fabien Le , Knaus Petra , Geissler Sven , Stricker Sigmar 
Published: July 2022

AbstractSkeletal muscle regeneration requires the coordinated interplay of diverse tissue-resident- and infiltrating cells. Fibro-adipogenic progenitors (FAPs) are an interstitial cell population that provides a beneficial microenvironment for muscle stem cells (MuSCs) during muscle regeneration. Here we show that the transcription factor Osr1 is essential for FAPs to communicate with MuSCs and infiltrating macrophages, thus coordinating muscle regeneration. Conditional inactivation of Osr1 impaired muscle regeneration with reduced myofiber growth and formation of excessive fibrotic tissue with reduced stiffness. Osr1-deficient FAPs acquired a fibrogenic identity with altered matrix secretion and cytokine expression resulting in impaired MuSC viability, expansion and differentiation. Immune cell profiling suggested a novel role for Osr1-FAPs in macrophage polarization. In vitro analysis suggested that increased TGFβ signaling and altered matrix deposition by Osr1-deficient FAPs actively suppressed regenerative myogenesis. In conclusion, we show that Osr1 is central to FAP function orchestrating key regenerative events such as inflammation, matrix secretion and myogenesis.
Local neuroplasticity in adult glaucomatous visual cortex
Authors: Carvalho Joana , Invernizzi Azzurra , Martins Joana , Renken Remco J. , Cornelissen Frans W. 
Published: July 2022

AbstractThe degree to which the adult human visual cortex retains the ability to functionally adapt to damage at the level of the eye remains ill-understood. Previous studies on cortical neuroplasticity primarily focused on the consequences of foveal visual field defects (VFD), yet these findings may not generalize to peripheral defects such as occur in glaucoma. Moreover, recent findings on neuroplasticity are often based on population receptive field (pRF) mapping, but interpreting these results is complicated in the absence of appropriate control conditions. Here, we used fMRI-based neural modeling to assess putative changes in pRFs associated with glaucomatous VFD. We compared the fMRI-signals and pRF estimates in participants with glaucoma to those of controls with case-matched simulated VFD. We found that the amplitude of the fMRI-signal is reduced in glaucoma compared to control participants and correlated with disease severity. Furthermore, while coarse retinotopic structure is maintained in all participants with glaucoma, we observed local pRF shifts and enlargements in early visual areas, relative to control participants. These differences imply that the adult brain retains local neuroplasticity. This finding has translational relevance, as it is consistent with VFD masking, which prevents glaucoma patients from noticing their VFD and seeking timely treatment.
Gamma (γ)-radiation stress response of the cyanobacterium Anabaena sp. PCC7120: Regulatory role of LexA and photophysiological changes
Authors: Srivastava Akanksha , Kumar Arvind , Biswas Subhankar , Kumar Rajender , Srivastava Vaibhav , Rajaram Hema , Mishra Yogesh 
Published: July 2022

AbstractHigh radioresistance of the cyanobacterium, Anabaena sp. PCC7120 has been attributed to efficient DNA repair, protein recycling, and oxidative stress management. However, the regulatory network involved in these batteries of responses remains unexplored. In the present study, the role of a global regulator, LexA in modulating gamma (γ)-radiation stress response of Anabaena was investigated. Comparison of the cytosolic proteome profiles upon γ-radiation in recombinant Anabaena strains, AnpAM (vector-control) and AnlexA+ (LexA-overexpressing), revealed 41 differentially accumulated proteins, corresponding to 29 distinct proteins. LexA was found to be involved in the regulation of 27 of the corresponding genes based on the presence of AnLexA-Box, EMSA, and/or qRT-PCR studies. The majority of the regulated genes were found to be involved in C-assimilation either through photosynthesis or C-catabolism and oxidative stress alleviation. Photosynthesis, measured in terms of PSII photophysiological parameters and thylakoid membrane proteome was found to be affected by γ-radiation in both AnpAM and AnlexA+ cells, with LexA affecting them even under control growth conditions. Thus, LexA functioned as one of the transcriptional regulators involved in modulating γ-radiation stress response in Anabaena. This study could pave the way for a deeper understanding of the regulation of γ-radiation-responsive genes in cyanobacteria at large.Highlightsγ-radiation alters PSII photophysiology and thylakoid proteome profile in Anabaena.LexA modulates the cytosolic and thylakoid proteome of Anabaena under γ-radiation.LexA functions as one of the regulators of radiation-responsive genes in Anabaena.
A quantitative rule to explain multi-spine plasticity
Authors: Chater T. E. , Eggl M. F. , Goda Y. , Tchumatchenko T. 
Published: July 2022

AbstractNeurons receive thousands of inputs onto their dendritic arbour, where individual synapses undergo activitydependent changes in strength. The durable forms of synaptic strength change, long-term potentiation (LTP) and long-term depression (LTD) require calcium entry through N-methyl-D-aspartate receptors (NMDARs) that triggers downstream protein signalling cascades in the dendrite. Notably, changes in postsynaptic strengths associated with LTP and LTD are correlated to changes in spine head volume, referred to as structural LTP (sLTP) and structural LTD (sLTD). Intriguingly, LTP and LTD, including sLTP and sLTD, are not necessarily restricted to the active, targeted synapses (homosynapses), and the changes in synaptic strength can spread and affect the strengths of inactive or non-stimulated synapses (heterosynapses) on the same cell. Moreover, the plasticity outcome at both homo- and heterosynapses can depend on the number of stimulated sites when eliciting multi-spine plasticity. Precisely how neurons allocate resources for implementing the changes in strength at individual synapses depending on their proximity to input activity across space and time remains an open question. In order to gain insights into the elementary processes underlying multi-spine plasticity that engages both homosynaptic and heterosynaptic changes, we have combined experimental and mathematical modelling approaches. On the one hand, we used glutamate uncaging to precisely and systematically stimulate variable numbers of homosynapses sharing the same dendritic branch whilst monitoring tens of other heterosynapses on the same dendrite. Homosynaptic potentiation of clusters of dendritic spines leads to heterosynaptic changes that are dependent on NMDAR, CaMKII and calcineurin. On the other hand, inspired by the Ca2+levels hypothesis where different amounts of Ca2+lead to either growth or shrinkage of spines, we have built a model based on a dual-role Ca2+-dependent protein that induces sLTP or sLTD. Comparing our experimental results with model predictions, we find that(i)both collaboration and competition among spines for protein resources are key drivers of heterosynaptic plasticity and(ii)the temporal and spatial distance between simultaneously stimulated spines impact the resulting spine dynamics. Moreover, our model can reconcile disparate experimental reports of sLTP and sLTD at homo- and heterosynaptic spines. Our results provide a quantitative description of the heterosynaptic footprint over minutes and hours post-stimulation across tens of microns of dendritic space. This broadens our knowledge about the operation of non-linear dendritic summation rules and how they impact spiking decisions.
Exploring the “theory is king” thesis in accounting research: the case of actor-network theory
Authors: Lukka Kari , Modell Sven , Vinnari Eija 
Published: July 2022

PurposeThis paper examines the influence of the normal science tradition, epitomized by the notion that “theory is king”, on contemporary accounting research and the epistemological tensions that may emerge as this idea is applied to particular ways of studying accounting. For illustrative purposes, the authors focus on research informed by actor-network theory (ANT) which can be seen as an “extreme case” in the sense that it is, in principle, difficult to reconcile with the normal science aspirations.Design/methodology/approachThe paper offers an analysis based on a close reading of how accounting scholars, using ANT, theorize, and if they do engage in explicit theorizing, how they deal with the tensions that might emerge from the need to reconcile its epistemological underpinnings with those of the normal science tradition.FindingsThe findings of this paper show that the tensions between normal science thinking and the epistemological principles of ANT have, in a few cases, been avoided, as researchers stay relatively faithful to ANT and largely refrain from further theory development. However, in most cases, the tensions have ostensibly been ignored as researchers blend the epistemology of ANT and that of normal science without reflecting on the implications of doing so.Originality/valueThe paper contributes to emerging debates on the role of the normal science tradition in contemporary accounting research, and also extends recent discussions on the role of theory in accounting research inspired by ANT. The paper proposes three reasons for the observed blending of epistemologies: unawareness of tensions, epistemological eclecticism and various political considerations.
Sociolinguistic repositories as asset: challenges and difficulties in Brazil
Authors: Meister Ko. Freitag Raquel 
Published: July 2022

PurposeThis paper aims to provide a context for Brazilian Portuguese language documentation and its data collection to establish linguistic repositories from a sociolinguistic overview.Design/methodology/approachThe main sociolinguistic projects that have generated collections of Brazilian Portuguese language data are presented.FindingsThe comparison with another situation of repositories (seed vaults) and with the accounting concept of assets is evocated to map the challenges to be overcome in proposing a standardized and professional language repository to host the collections of linguistic data arising from the reported projects and others, in the accordance with the principles of the open science movement.Originality/valueThinking about the sustainability of projects to build linguistic documentation repositories, partnerships with the information technology area, or even with private companies, could minimize problems of obsolescence and safeguarding of data, by promoting the circulation and automation of analysis through natural language processing algorithms. These planning actions may help to promote the longevity of the linguistic documentation repositories of Brazilian sociolinguistic research.
Intelligent personal assistant for personal computers using long short-term memory-based verbalizer
Authors: Swamidason Iwin Thanakumar Joseph , Tatiparthi Sravanthy , Velswamy Karunakaran , Velliangiri S. 
Published: July 2022

PurposeAn intelligent personal assistant for personal computers (PCs) is a vital application for the current generation. The current computer personal assistant services checking frameworks are not proficient at removing significant data from PCs and long-range informal communication information.Design/methodology/approachThe proposed verbalizers use long short-term memory to classify the user task and give proper guidelines to the users. The outcomes show that the proposed method determinedly handles heterogeneous information and improves precision. The main advantage of long short-term memory is that handle the long-term dependencies in the input data.FindingsThe proposed model gives the 22% mean absolute error. The proposed method reduces mean square error than support vector machine (SVM), convolutional neural network (CNN), multilayer perceptron (MLP) and K-nearest neighbors (KNN).Originality/valueThis paper fulfills the necessity of intelligent personal assistant for PCs using verbalizer.