bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Dose-Response Model and D10-Value forMycobacterium tuberculosisExposed to Dosimetrically Verified Ionizing Radiation
Authors: Watkins Jackson V , Bell Justin , Knabenbauer Phillip , Brandl Alexander , Dobos Karen M 
Published: March 2021

AbstractTechniques for pathogen inactivation have been employed by laboratories to help ease the financial, physical, and health strains associated with (A)BSL-3 work. Exposure to radiation is the most common and useful of these methods to inactivate pathogens grown in large-scale culture. While robust protocols exist for radiation exposure techniques, there are variances in methods used to determine the radiation dose and dose rate required to inactivate pathogens. Furthermore, previous studies often do not include radiation dosimetry verification or address corresponding dosimetry uncertainties for dose response-assays. Accordingly, this study was conducted with the purpose of completing a dosimetry assessment of the radiation field within the sample chamber of a sealed source irradiator, to subsequently determine the radiation dose required to inactivate pathogenic cultures. Physical dosimetry techniques (Fricke dosimetry, ion chamber measurements, and measurements with thermoluminescent dosimeters) were used to measure dose rate and rate variances within the sample chamber. By comparing the variances between the dosimetry methodologies and measurements, an estimated dose rate within the sample chamber was determined. The results of the dosimetry evaluation were used to determine the radiation dose samples ofMycobacterium tuberculosisreceived, to accurately associate biological markers of inactivation to specific doses of ionizing radiation. A D10value and dose-response curve were developed to describe the inactivation ofMtbfrom increasing doses of ionizing radiation. The D10value is experimentally relevant for comparative analysis and potentially provides a biological baseline for inactivation verification. This methodology can also easily be translated to other pathogen models.ImportanceThis work set out to give us a better understanding of how much radiation is required to inactivateMycobacterium tuberculosis, the bacteria that causes tuberculosis disease. Radiation dose from a source is not something that can just be inputted, it must be calculated, so we also determined the approximate dose from the source to address ambiguities that had previously existed while inactivating microbes. We were able to generate an accurate description of inactivation ofMycobacterium tuberculosisby correlating it with a value representing 90% death of the treated cells. We also unexpectedly discovered that very low levels of radiation increase certain activity within the cell. This is important because it allows us to better understand how radiation killsMycobacterium tuberculosis, and gives us a value to compare to other organisms. It also offers other researchers a method to use under their own specific conditions.
Evidence of post-domestication hybridization and adaptive introgression in Western European grapevine varieties
Authors: Freitas S. , Gazda M.A. , Rebelo M. , Muñoz-Pajares A.J. , Vila-Viçosa C. , Muñoz-Mérida A. , Gonçalves L.M. , Azevedo-Silva D. , Afonso S. , Castro I. , Castro P.H. , Sottomayor M. , Beja-Pereira A. , Tereso J. , Ferrand N. , Gonçalves E. , Martins A. , Carneiro M. , Azevedo H. 
Published: March 2021

ABSTRACTGrapevine (Vitis viniferaL.) is one of the most significant crops in the world. Today’s richness in grapevine diversity results from a complex domestication history over multiple historical periods. Here, we employed whole genome resequencing to elucidate different aspects of the recent evolutionary history of this crop. Our results support a model in which a central domestication event in grapevine was followed by post-domestication hybridization with local wild genotypes, leading to the presence of an introgression signature in modern wine varieties across Western Europe. The strongest signal was associated with a subset of Iberian grapevine varieties, which show large introgression tracts. We targeted this study group for further analysis, demonstrating how regions under selection in wild populations from the Iberian Peninsula were preferentially passed on to the cultivated varieties by geneflow. Examination of underlying genes suggests that environmental adaptation played a fundamental role in both the evolution of wild genotypes and the outcome of hybridization with cultivated varieties, supporting a case of adaptive introgression in grapevine.
Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI
Authors: Choi Sangcheon , Zeng Hang , Chen Yi , Sobczak Filip , Qian Chunqi , Yu Xin 
Published: March 2021

ABSTRACTLaminar BOLD-fMRI has been applied to better depict the neuronal input and output circuitry and functional connectivity across cortical layers by measuring local hemodynamic changes. Despite extensive studies detecting laminar fMRI signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across different cortical regions remain to be fully investigated in both evoked and resting states. Here, we developed a multi-slice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 µm) and temporal resolution (100 ms) in anesthetized rats. Across different scanning trials, we detected both laminar-specific positive and negative BOLD responses in the surrounding cortical region adjacent to the most activated cortex under evoked condition. Specifically, in contrast to the typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for the trials with negative BOLD in adjacent regions, which indicate a brain state-dependent laminar-fMRI responses based on cortiocotical interaction from different trials. Also, we acquired the laminar-specific rs-fMRI signals across different cortical regions, of which the high spatiotemporal resolution allows us to estimate lag times based on the maximal cross-correlation of laminar-specific rs-fMRI signals. In contrast to the larger variability of lag times in L1 and 6, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from the caudal to the rostral slice. In summary, our work provides a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity with MS-LS, presenting layer-specific spatiotemporal variation of both evoked and rs-fMRI signals.
Loneliness and the social brain: how perceived social isolation impairs human interactions
Authors: Lieberz Jana , Shamay-Tsoory Simone G. , Saporta Nira , Esser Timo , Kuskova Ekaterina , Stoffel-Wagner Birgit , Hurlemann René , Scheele Dirk 
Published: March 2021

AbstractLoneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, we use a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n= 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n= 40). Moreover, lonely individuals are rated as less trustworthy compared to controls and identified by the blinded confederate better than chance. During initial trust decisions, lonely individuals exhibit attenuated limbic and striatal activation and blunted functional connectivity between the anterior insula and occipitoparietal regions, which correlates with the diminished affective responsiveness to the positive social interaction. This neural response pattern is not mediated by loneliness-associated psychological symptoms. Thus, our results indicate compromised integration of trust-related information as a shared neurobiological component in loneliness, yielding a reciprocally reinforced trust bias in social dyads.
Contribution of epigenetic changes to escape from X-chromosome inactivation
Authors: Balaton Bradley P. , Brown Carolyn J. 
Published: March 2021

AbstractBackgroundX-chromosome inactivation (XCI) is the epigenetic inactivation of one of two X chromosomes in XX eutherian mammals. The facultatively heterochromatic inactive X chromosome acquires many chromatin changes including DNA methylation and histone modifications. Despite these changes, some genes escape or variably escape from inactivation, and to the extent that they have been studied, epigenetic marks correlate with expression.ResultsWe downloaded data from the International Human Epigenome Consortium and compared previous XCI status calls to DNA methylation, H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3. At genes subject to XCI we found heterochromatic marks enriched, and euchromatic marks depleted on the inactive X when compared to the active X. Similar results were seen for genes escaping XCI although with diminished effect with H3K27me3 being most enriched. Using sample-specific XCI status calls made using allelic expression or DNA methylation we also compared differences between samples with opposite XCI statuses at variably escaping genes. We found some marks significantly differed with XCI status, but which marks were significant was not consistent between genes. We trained a model to predict XCI status from these epigenetic marks and obtained over 75% accuracy for genes escaping and over 90% for genes subject to XCI. This model allowed us to make novel XCI status calls for genes without allelic differences or CpG islands required for other XCI status calling methods. Using these calls to examine a domain of variably escaping genes, we saw XCI status vary at the level of individual genes and not at the domain level.ConclusionHere we show that epigenetic marks differ between genes that are escaping and those subject to XCI, and that genes escaping XCI still differ between the active and inactive Xs. We show epigenetic differences at variably escaping genes, between samples escaping and those subject to XCI. Lastly we show gene-level regulation of variably escaping genes within a domain.
Extensive structural remodeling of the axonal arbors of parvalbumin basket cells during development
Authors: Micheva Kristina D. , Kiraly Marianna , Perez Marc M. , Madison Daniel V. 
Published: March 2021

AbstractParvalbumin-containing (PV+) basket cells are specialized cortical interneurons that regulate the activity of local neuronal circuits with high temporal precision and reliability. PV+ interneuron disfunction is associated with numerous psychiatric disorders, including schizophrenia and autism spectrum disorders. To understand how the PV+ interneuron connectivity underlying their functional properties is established during development, we used array tomography to map pairs of synaptically connected PV+ interneurons and postsynaptic neurons from the neocortex of mice of both sexes. We focused on the axon-myelin unit of the PV+ interneuron and quantified the number of synapses onto the postsynaptic neuron, length of connecting axonal paths, and their myelination at different time points between 2 weeks and 7 months of age. We find that myelination of the proximal axon occurs very rapidly during the third postnatal week and precedes a massive synapse pruning which takes place in the 4th postnatal week leading to about three-fold reduction of synaptic contacts made by the PV+ interneuron on its postsynaptic partner. Autapses, the synapses that PV+ interneurons form on themselves, however, are not subjected to pruning. Axon reorganizations continue beyond postnatal month 2, with the postsynaptic targets of PV+ interneurons gradually shifting to more proximal locations, and the length of axonal paths and their myelin becoming conspicuously uniform per connection. These continued microcircuit refinements likely provide the structural substrate for the robust inhibitory effects and fine temporal precision of PV+ basket cells.Significance statementThe axon of adult parvalbumin-containing (PV+) interneurons is highly specialized for fast and reliable neurotransmission. It is myelinated and forms synapses mostly onto the cell bodies and proximal dendrites of postsynaptic neurons for maximal impact. In this study we follow the development of the PV+ interneuron axon, its myelination and synapse formation, revealing a rapid sequence of axonal reorganization, myelination of the PV+ interneuron proximal axon, and subsequent pruning of almost two-thirds of the synapses in an individual connection. This is followed by a prolonged period of axon refinement and additional myelination leading to a remarkable precision of connections in the adult mouse cortex, consistent with the temporal precision and fidelity of PV+ interneuron action.
Interstitial leukocyte navigation through a search and run response to gradients
Authors: Georgantzoglou Antonios , Poplimont Hugo , Lämmermann Tim , Sarris Milka 
Published: March 2021

AbstractMigrating cells must interpret chemical gradients to guide themselves within tissues. A general premise has been that gradients influence the direction of leading-edge protrusions. However, recent evidence indicates that actin flows correlate better with directed motion than protrusions. A unified chemotaxis model that integrates the role of protrusions and actin flows and that accounts forin vivocell motion patterns is lacking. Here, we provide direct experimental evidence of how neutrophils sense gradients in real-timein vivoand demonstrate a two-stage process: first a ‘search’ phase, that requires actin network expansion by Arp2/3, whereby cells slow down, explore the environment and execute path corrections. This is followed by a ‘run’ phase, that requires Myosin-II-driven contractility and fast actin flows, whereby cells accelerate and persist in the source direction. Thus, protrusive forces support chemotaxis by enhancing signal detection, while actin flows act as the ultimate output of gradient processing.
Recapitulate Human Cardio-pulmonary Co-development Using Simultaneous Multilineage Differentiation of Pluripotent Stem Cells
Authors: Hoe Ng Wai , Johnston Elizabeth K. , Jie Tan Jun , Bliley Jacqueline M. , Feinberg Adam W. , Stolz Donna B. , Sun Ming , Hawkins Finn , Kotton Darrell N. , Ren Xi 
Published: March 2021

AbstractThe extensive crosstalk between the developing heart and lung is pivotal for their proper morphogenesis and maturation. However, there remains a lack of model systems for investigating the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human pluripotent stem cells (hPSCs) via temporal specific tuning of WNT and TGF-β signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (μTs), and observed expedited alveolar maturation in the presence of cardiac accompany. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage μT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect our multilineage differentiation model to offer an experimentally tractable system for investigating human cardio-pulmonary interplay and tissue boundary formation during embryogenesis.
Development and validation of FootNet; a new kinematic algorithm to improve foot-strike and toe-off detection in treadmill running
Authors: Rivadulla Adrian Rodriguez , Chen Xi , Weir Gillian , Cazzola Dario , Trewartha Grant , Hamill Joseph , Preatoni Ezio 
Published: March 2021

AbstractThe accurate detection of foot-strike and toe-off is often critical in the assessment of running biomechanics. The gold standard method for step event detection requires force data which are not always available. Although kinematics-based algorithms can also be used, their accuracy and generalisability are limited, often requiring corrections for speed or foot-strike pattern. The purpose of this study was to develop FootNet, a novel kinematics and deep learning-based algorithm for the detection of step events in treadmill running. Five treadmill running datasets were gathered and processed to obtain segment and joint kinematics, and to identify the contact phase within each gait cycle using force data. The proposed algorithm is based on a long short-term memory recurrent neural network and takes the distal tibia anteroposterior velocity, ankle dorsiflexion/plantar flexion angle and the anteroposterior and vertical velocities of the foot centre of mass as input features to predict the contact phase within a given gait cycle. The chosen model architecture underwent 5-fold cross-validation and the final model was tested in a subset of participants from each dataset (30%). Non-parametric Bland-Altman analyses (bias and [95% limits of agreement]) and root mean squared error (RMSE) were used to compare FootNet against the force data step event detection method. The association between detection errors and running speed, foot-strike angle and incline were also investigated. FootNet outperformed previously published algorithms (foot-strike bias = 0 [-10, 7] ms, RMSE = 5 ms; toe-off bias = 0 [-10, 10] ms, RMSE = 6 ms; and contact time bias = 0 [-15, 15] ms, RMSE = 8 ms) and proved robust to different running speeds, foot-strike angles and inclines. We have made FootNet’s source code publicly available for step event detection in treadmill running when force data are not available.
PPIDomainMiner : Inferring domain-domain interactions from multiple sources of protein-protein interactions
Authors: Alborzi Seyed Ziaeddine , Ahmed Nacer Amina , Najjar Hiba , Ritchie David W , Devignes Marie-Dominique 
Published: March 2021

AbstractMany biological processes are mediated by protein-protein interactions (PPIs). Because protein domains are the building blocks of proteins, PPIs likely rely on domain-domain interactions (DDIs). Several attempts exist to infer DDIs from PPI networks but the produced datasets are heterogeneous and sometimes not accessible, while the PPI interactome data keeps growing.We describe a new computational approach called “PPIDM” (Protein-Protein Interactions Domain Miner) for inferring DDIs using multiple sources of PPIs. The approach is an extension of our previously described “CODAC” (Computational Discovery of Direct Associations using Common neighbors) method for inferring new edges in a tripartite graph. The PPIDM method has been applied to seven widely used PPI resources, using as “Gold-Standard” a set of DDIs extracted from 3D structural databases. Overall, PPIDM has produced a dataset of 84, 552 non-redundant DDIs. Statistical significance (p-value) is calculated for each source of PPI and used to classify the PPIDM DDIs in Gold (9,175 DDIs), Silver (24, 934 DDIs) and Bronze (50, 443 DDIs) categories. Dataset comparison reveals that PPIDM has inferred from the 2017 releases of PPI sources about 46% of the DDIs present in the 2020 release of the 3did database, not counting the DDIs present in the Gold-Standard. The PPIDM dataset contains 10, 229 DDIs that are consistent with more than 13, 300 PPIs extracted from the IMEx database, and nearly 23,300 DDIs (27.5%) that are consistent with more than 214,000 human PPIs extracted from the STRING database. Examples of newly inferred DDIs covering more than 10 PPIs in the IMEx database are provided.Further exploitation of the PPIDM DDI reservoir includes the inventory of possible partners of a protein of interest and characterization of protein interactions at the domain level in combination with other methods. The result is publicly available athttp://ppidm.loria.fr/.Author summaryWe revisit at a large scale the question of inferring DDIs from PPIs. Compared to previous studies, we take a unified approach accross multiple sources of PPIs. This approach is a method for inferring new edges in a tripartite graph setting and can be compared to link prediction approaches in knowledge graphs. Aggregation of several sources is performed using an optimized weighted average of the individual scores calculated in each source. A huge dataset of over 84K DDIs is produced which far exceeds the previous datasets. We show that a significant portion of the PPIDM dataset covers a large number of PPIs from curated (IMEx) or non curated (STRING) databases. Such a reservoir of DDIs deserves further exploration and can be combined with high-throughput methods such as cross-linking mass spectrometry to identify plausible protein partners of proteins of interest.
A new triple fluorescence reporter system for discrimination of Apobec1 and Apobec3 C-to-U RNA editing activities and editing-dependent protein expression
Authors: Schweissthal Barbara , Brunken Kea , Brach Julia , Emde Leonie , Hetsch Florian , Fricke Steffen , Meier Jochen C. 
Published: March 2021

AbstractThe human body is composed of many different cell types which communicate with each other. In particular, the brain consists of billions of neurons and non-neuronal cells which are interconnected and require tight and precise regulation of cellular processes. RNA editing is a cellular process that diversifies gene function by enzymatic deamination of cytidine or adenine. This can result in changes of protein structure and function. Altered RNA editing is becoming increasingly associated with all kind of disease, but most approaches use advanced sequencing technologies to analyze bulk material. However, it is also becoming progressively evident that changes in RNA editing have to be analyzed and considered in a cell type specific way. We present here a triple fluorescence reporter system that discriminates between Apobec1- and Apobec3-dependent C-to-U RNA editing at the single cell level. In particular, the Apobec3 reporter enables C-to-U RNA editing inducible protein expression through generation of a RNA splice donor site. We used the new system here to analyze Apobec1- and Apobec3-dependent RNA editing in primary neuron culture. The results reveal a large heterogeneity of C-to-U RNA editing in neurons and glia cells, and they show that GABAergic neurons are not able to perform Apobec1-dependent RNA editing, but Apobec3-dependent editing. Altogether, the new system can be the foundation of therapeutic application systems that counteract changes in Apobec3-dependent RNA editing in disease while simultaneously monitoring Apobec1-dependent RNA editing at the single cell level.