bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative cell entry mechanisms for SARS-CoV-2 and multiple animal viruses
Authors: Ojha Ravi , Jiang Anmin , Mäntylä Elina , Modhira Naphak , Witte Robert , Gaudin Arnaud , De Zanetti Lisa , Gormal Rachel , Vihinen-Ranta Maija , Mercer Jason , Suomalainen Maarit , Greber Urs F. , Yamauchi Yohei , Yves-Lozach Pierre , Helenius Ari , Vapalahti Olli , Young Paul , Watterson Daniel , Meunier Frédéric A. , Joensuu Merja , Balistreri Giuseppe 
Published: July 2023

AbstractThe cell entry mechanism of SARS-CoV-2, the causative agent of the COVID-19 pandemic, is not fully understood. Most animal viruses hijack cellular endocytic pathways as an entry route into the cell. Here, we show that in cells that do not express serine proteases such as TMPRSS2, genetic depletion of all dynamin isoforms blocked the uptake and strongly reduced infection with SARS-CoV-2 and its variant Delta. However, increasing the viral loads partially and dose-dependently restored infection via a thus far uncharacterized entry mechanism. Ultrastructural analysis by electron microscopy showed that this dynamin-independent endocytic processes appeared as 150-200 nm non-coated invaginations and was efficiently used by numerous mammalian viruses, including alphaviruses, influenza, vesicular stomatitis, bunya, adeno, vaccinia, and rhinovirus. Both the dynamin-dependent and dynamin-independent infection of SARS-CoV-2 required a functional actin cytoskeleton. In contrast, the alphavirus Semliki Forest virus, which is smaller in diameter, required actin only for the dynamin-independent entry. The presence of TMPRSS2 protease rescued SARS-CoV-2 infection in the absence of dynamins. Collectively, these results indicate that some viruses such as canine parvovirus and SARS-CoV-2 mainly rely on dynamin for endocytosis-dependent infection, while other viruses can efficiently bypass this requirement harnessing an alternative infection entry route dependent on actin.
The architecture of multifunctional ecological networks
Authors: Hervías-Parejo Sandra , Cuevas-Blanco Mar , Lacasa Lucas , Traveset Anna , Donoso Isabel , Heleno Ruben , Nogales Manuel , Rodríguez-Echeverría Susana , Melián Carlos , Eguíluz Victor M. 
Published: July 2023

AbstractUnderstanding how biotic interactions affect ecosystem functioning has been a research priority in natural sciences due to their critical role in bolstering ecological resilience1–3. Yet, traditional assessment of ecological complexity typically focus on species-species effective interactions that mediate a particular function (e.g. pollination4or seed dispersal5), overlooking the synergistic effect of multiple functions that further underpin species-function and function-function interactions in multifunctional ecosystems. At the same time, while ecological network theory holds a potential to quantify the relationship between biodiversity and ecosystem multifunctionality6, 7, its connection has been done mainly conceptually, due to challenges measuring different interactions and establishing their relevance across multiple niche dimensions8, 9. Such lack of quantitative studies therefore limits our ability to determine which species and interactions are important to maintain the multiple functions of ecosystems10. Here we develop a framework –derived from a resource-consumer-function tensor analysis-that bridges these gaps by framing biodiversity-ecosystem multifunctionality in terms of multilayer ecological network theory. Its application to recently collected ecological data –– reporting weighted interactions between plants, animals and fungi across multiple function types––allows to (i) unveil and quantify the existence of both (multi-functional) keystone species and a dual function keystoneness pattern, and (ii) project plants and functions into a similarity space where clear clusters emerge and the importance of weak links is manifested. This dual insight from species and functional perspectives will better guide conservation efforts to reduce biodiversity loss.
Hiding in the bush, in fear of a predator! Vegetation and predators influence shoaling among wild zebrafish
Authors: Mukherjee Ishani , Bhat Anuradha 
Published: July 2023

AbstractSocial responses of aquatic group-living organisms are critically dependent on predation risk and vegetation cover in their habitat. To gain insight into how these factors shape their immediate responses, we exposed wild zebrafish shoals to either vegetation, predator cues or both these factors simultaneously. Control treatments were not exposed to the above factors. By analyzing 60 unique shoals across 270 experimental trials, we found that while shoals formed significantly larger subgroups and were significantly more polarized in the presence of predator cues, both these properties decreased when shoals experienced predator cues in presence of vegetation. Furthermore, foraging was significantly lower when predator cues and/or vegetation were present. Tracking of all individuals in treatments devoid of vegetation revealed that: (i) compared to control treatments, individuals within shoals receiving predator cues had a significantly higher probability to continue being in a group and (ii) individuals occupying the front positions deviated lesser from their median position within a shoal as compared to other individuals. Anti-predator responses and foraging are critical for survival and therefore, this study provides important insights into shoal dynamics in changing environments.
Role of Articulatory Motor Networks in Perceptual Categorization of Speech Signals: A 7 T fMRI Study
Authors: Lankinen Kaisu , Ahveninen Jyrki , Uluç Işıl , Daneshzand Mohammad , Mareyam Azma , Kirsch John E. , Polimeni Jonathan R. , Healy Brian C. , Tian Qiyuan , Khan Sheraz , Nummenmaa Aapo , Wang Qing-mei , Green Jordan R. , Kimberley Teresa J. , Li Shasha 
Published: July 2023

BACKGROUNDThe association between brain regions involved in speech production and those that play a role in speech perception is not yet fully understood. We compared speech production related brain activity with activations resulting from perceptual categorization of syllables using high field 7 Tesla functional magnetic resonance imaging (fMRI) at 1-mm isotropic voxel resolution, enabling high localization accuracy compared to previous studies.METHODSBlood oxygenation level dependent (BOLD) signals were obtained in 20 normal hearing subjects using a simultaneous multi-slice (SMS) 7T echo-planar imaging (EPI) acquisition with whole-head coverage and 1 mm isotropic resolution. In aspeech production localizertask, subjects were asked to produce a silent lip-round vowel /u/ in response to the visual cue “U” or purse their lips when they saw the cue “P”. In aphoneme discrimination task, subjects were presented with pairs of syllables, which were equiprobably identical or different along an 8-step continuum between the prototypic /ba/ and /da/ sounds. After the presentation of each stimulus pair, the subjects were asked to indicate whether the two syllables they heard were identical or different by pressing one of two buttons. In aphoneme classification task, the subjects heard only one syllable and asked to indicate whether it was /ba/ or /da/.RESULTSUnivariate fMRI analyses using a parametric modulation approach suggested that left motor, premotor, and frontal cortex BOLD activations correlate with phoneme category variability in the /ba/–/da/ discrimination task. In contrast, the variability related to acoustic features of the phonemes were the highest in the right primary auditory cortex. Our multivariate pattern analysis (MVPA) suggested that left precentral/inferior frontal cortex areas, which were associated with speech production according to the localizer task, play a role also in perceptual categorization of the syllables.CONCLUSIONSThe results support the hypothesis that articulatory motor networks in the left hemisphere that are activated during speech production could also have a role in perceptual categorization of syllables. Importantly, high voxel-resolution combined with advanced coil technology allowed us to pinpoint the exact brain regions involved in both perception and production tasks.
Distinct groups of RNA viruses associated with thermoacidophilic bacteria
Authors: Urayama Syun-ichi , Fukudome Akihito , Hirai Miho , Okumura Tomoyo , Nishimura Yosuke , Takaki Yoshihiro , Kurosawa Norio , Koonin Eugene V. , Krupovic Mart , Nunoura Takuro 
Published: July 2023

AbstractRecent massive metatranscriptome mining substantially expanded the diversity of the bacterial RNA virome, suggesting that additional groups of riboviruses infecting bacterial hosts remain to be discovered. We employed full length double-stranded (ds) RNA sequencing for identification of riboviruses associated with microbial consortia dominated by bacteria and archaea in acidic hot springs in Japan. Whole sequences of two groups of multisegmented riboviruses genomes were obtained. One group, which we denoted hot spring riboviruses (HsRV), consists of unusual viruses with distinct RNA-dependent RNA polymerases (RdRPs) that seem to be intermediates between typical ribovirus RdRPs and viral reverse transcriptases. We also identified viruses encoding HsRV-like RdRPs in moderate aquatic environments, including marine water, river sediments and salt marsh, indicating that this previously overlooked ribovirus group is not restricted to the extreme ecosystem. The HsRV-like viruses are candidates for a distinct phylum or even kingdom within the viral realmRiboviria. The second group, denoted hot spring partiti-like viruses (HsPV), is a distinct branch within the familyPartitiviridae. All genome segments in both these groups of viruses display the organization typical of bacterial riboviruses, where multiple open reading frames encoding individual proteins are preceded by ribosome-binding sites. Together with the identification in bacteria-dominated habitats, this genome architecture indicates that riboviruses of these distinct groups infect thermoacidophilic bacterial hosts.
Impact of PET reconstruction on Aβ-amyloid quantitation in cross-sectional and longitudinal analyses
Authors: Ruwanpathirana Gihan P. , Williams Robert C. , Masters Colin L. , Rowe Christopher C. , Johnston Leigh A. , Davey Catherine E. 
Published: July 2023

AbstractAmyloid beta (Aβ) accumulation in Alzheimer’s disease (AD) is typically measured using standardized uptake value ratio (SUVR) and the Centiloid scale (CL). The low spatial resolution of PET images is known to degrade quantitative metrics due to the partial volume effect (PVE). This paper examines the impact of spatial resolution, as determined by the reconstruction configuration, on the Aβ-PET quantitation in both cross-sectional and longitudinal data.MethodsCross-sectional Study-89 subjects with [18F]-florbetapir scans (44 Aβ-, 45 Aβ+) were reconstructed using 69 reconstruction configurations. For each reconstruction, Aβ SUVR was calculated and the spatial resolution was calculated as full-width-at-half-maximum (FWHM) using the barrel phantom method (Lodgeet al, 2018). The change of SUVR and the effect size of the difference in SUVR between Aβ- and Aβ+ groups with FWHM were examined.Longitudinal study-79 subjects (46 Aβ-, 33 Aβ+) with three [18F]-flutemetamol scans were analysed. All scans were reconstructed using low-, medium- and high-resolution reconstruction configurations and Aβ CLs were calculated. Since linear Aβ accumulation was assumed over a 10-year interval, for each reconstruction configuration, Aβ accumulation rate differences (ARD) between the second and first periods were calculated for all the subjects and compared. Zero ARD was used as a consistency metric. The number of Aβ-accumulators was also used to compare reconstruction configurations.ResultsCross-sectional-SUVRs in both Aβ- and Aβ+ groups were impacted by the FWHM of the reconstruction method; Aβ- SUVRs increased for FWHM ≥ 4.5 mm, while Aβ+ SUVRs decreased across the FWHM range. High-resolution reconstructions provided the best statistical separation between groups.Longitudinal study-In the Aβ-group, the median ARD of low-resolution reconstructed data was greater than zero whereas the ARDs of higher-resolution reconstructions were not significantly different to zero, indicating less consistent rates in the low-than the higher-resolution data. Higher-resolution reconstructions identified 10 additional Aβ-accumulators in the Aβ-group, resulting in a 22% increased group size compared to the low-resolution reconstructions. Higher-resolution reconstructions reduced the average CL values of the negative group by 12 points.ConclusionsHigh-resolution PET reconstructions, inherently less impacted by PVE, may improve Aβ-PET quantitation in both cross-sectional and longitudinal data. In the cross-sectional analysis, separation of Aβ groups’ SUVRs increased with spatial resolution. Longitudinal analysis showed better Aβ accumulation consistency in higher-resolution compared to low-resolution reconstructions. The identification of more Aβ-accumulators from the higher-resolution reconstruction may be helpful in early-stage AD therapies.
Modelling population genetic screening in rare neurodegenerative diseases
Authors: Spargo Thomas P , Iacoangeli Alfredo , Ryten Mina , Forzano Francesca , Pearce Neil , Al-Chalabi Ammar 
Published: July 2023

AbstractImportanceGenomic sequencing enables rapid identification of a breadth of genetic variants. For clinical purposes, sequencing for small genetic variations is considered a solved problem, while challenges remain for structural variants given the lower sensitivity and specificity. Interest has recently risen among governing bodies in developing protocols for population-wide genetic screening. However, usefulness is constrained when the probability of being affected by a rare disease remains low despite a positive genetic test. This is a common scenario in neurodegenerative disorders. The problem is recognised among statisticians and statistical geneticists but less well understood by clinicians and researchers who will act on these results, and by the general public who might access screening services directly without the appropriate support for interpretation.ObservationsWe explore the probability of subsequent disease following genetic screening of several of variants, both single nucleotide variants (SNVs) and larger repeat expansions, for two neurological conditions, Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), comparing with screening for phenylketonuria which is well established. The risk following a positive screening test was 0.5% forC9orf72in ALS and 0.4% forHTTin HD, when testing repeat expansions for which the test had sub-optimal performance (sensitivity=99% and specificit =90%), and 12.7% for phenylketonuria and 10.9% for ALS SOD1, when testing pathogenic SNVs (sensitivity=99.96% and specificity=99.95%). Subsequent screening confirmation via PCR for C9orf72 led to a 2% risk of developing ALS as a result of the reduced penetrance (44%).Conclusions and RelevanceWe show that risk following a positive screening test result can be strikingly low for rare neurological diseases. Accordingly, to maximise the utility of screening, it is vital to prioritise protocols of very high sensitivity and specificity, careful selection of markers for screening, giving regard to clinical interpretability, actionability, high penetrance, and secondary testing to confirm positive findings.
Stimulus-dependent functional network topology in mouse visual cortex
Authors: Tang Disheng , Zylberberg Joel , Jia Xiaoxuan , Choi Hannah 
Published: July 2023

AbstractInformation is processed by networks of neurons in the brain. On the timescale of sensory processing, those neuronal networks have relatively fixed anatomical connectivity, while functional connectivity, which defines the interactions between neurons, can vary depending on the ongoing activity of the neurons within the network. We thus hypothesized that different types of stimuli, which drive different neuronal activities in the network, could lead those networks to display stimulus-dependent functional connectivity patterns. To test this hypothesis, we analyzed electrophysiological data from the Allen Brain Observatory, which utilized Neuropixels probes to simultaneously record stimulus-evoked activity from hundreds of neurons across 6 different regions of mouse visual cortex. The recordings had single-cell resolution and high temporal fidelity, enabling us to determine fine-scale functional connectivity. Comparing the functional connectivity patterns observed when different stimuli were presented to the mice, we made several nontrivial observations. First, while the frequencies of different connectivity motifs (i.e., the patterns of connectivity between triplets of neurons) were preserved across stimuli, the identities of the neurons within those motifs changed. This means that functional connectivity dynamically changes along with the input stimulus, but does so in a way that preserves the motif frequencies. Secondly, we found that the degree to which functional modules are contained within a single brain region (as opposed to being distributed between regions) increases with increasing stimulus complexity. This suggests a mechanism for how the brain could dynamically alter its computations based on its inputs. Altogether, our work reveals unexpected stimulus-dependence to the way groups of neurons interact to process incoming sensory information.
ReTrace: Topological evaluation of white matter tractography algorithms using Reeb graphs
Authors: Shailja S. , Chen Jefferson W. , Grafton Scott T. , Manjunath B.S. 
Published: July 2023

AbstractWe present ReTrace, a novel graph matching-based topological evaluation and validation method for tractography algorithms. ReTrace uses a Reeb graph whose nodes and edges capture the topology of white matter fiber bundles. We evaluate the performance of 96 algorithms from the ISMRM Tractography Challenge and the the standard algorithms implemented in DSI Studio for the population-averaged Human Connectome Project (HCP) dataset. The existing evaluation metrics such as the f-score, bundle overlap, and bundle overreach fail to account for fiber continuity resulting in high scores even for broken fibers, branching artifacts, and mis-tracked fiber crossing. In contrast, we show that ReTrace effectively penalizes the incorrect tracking of fibers within bundles while concurrently pinpointing positions with significant deviation from the ground truth. Based on our analysis of ISMRM challenge data, we find that no single algorithm consistently outperforms others across all known white matter fiber bundles, highlighting the limitations of the current tractography methods. We also observe that deterministic tractography algorithms perform better in tracking the fundamental properties of fiber bundles, specifically merging and splitting, compared to probabilistic tractography. We compare different algorithmic approaches for a given bundle to highlight the specific characteristics that contribute to successful tracking, thus providing topological insights into the development of advanced tractography algorithms.
Time-, tissue- and treatment-associated heterogeneity in tumour-residing migratory DCs
Authors: Lee Colin YC , Kennedy Bethany C , Richoz Nathan , Dean Isaac , Tuong Zewen K , Gaspal Fabrina , Li Zhi , Willis Claire , Hasegawa Tetsuo , Whiteside Sarah K , Posner David A , Carlesso Gianluca , Hammond Scott A , Dovedi Simon J , Roychoudhuri Rahul , Withers David R , Clatworthy Menna R 
Published: July 2023

AbstractTumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to a maturation programme enriched in regulatory molecule expression, including PD-L1, termed mRegDC. However, the spatio- temporal dynamics and role of mRegDCs in anti-tumour immune responses remain unclear. Using photoconvertible mice to precisely track DC migration, we found that mRegDCs were the dominant DC population arriving in the dLN, but a subset remained tumour-resident despite CCR7 expression. These tumour-retained mRegDCs were phenotypically and transcriptionally distinct from their dLN counterparts and were heterogeneous. Specifically, they demonstrated a progressive reduction in the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour mRegDCs spatially co-localised with PD-1+CD8+T cells in human and murine solid tumours. Following anti-PD-L1 treatment, tumour-residing mRegDCs adopted a state enriched in lymphocyte stimulatory molecules, including OX40L, which was capable of augmenting anti- tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in mRegDCs that may underpin a variable capacity to support intratumoural cytotoxic T cells, and provide insights into their role in cancer immunotherapy.
Single-cell analysis of signalling and transcriptional responses to type I interferons
Authors: Rigby Rachel E. , Rue-Albrecht Kevin , Sims David , Rehwinkel Jan 
Published: July 2023

SummaryType I interferons (IFNs) play crucial roles in antiviral defence, autoinflammation and cancer immunity. The human genome encodes 17 different type I IFNs that all signal through the same receptor. Non-redundant functions have been reported for some type I IFNs. However, whether different type I IFNs induce different responses remains largely unknown. We stimulated human peripheral blood mononuclear cells (PBMCs) with recombinant type I IFNs to address this question in multiple types of primary cells. We analysed signalling responses by mass cytometry and changes in gene expression by bulk and single-cell RNA sequencing. We found cell-type specific changes in the phosphorylation of STAT transcription factors and in the gene sets induced and repressed upon type I IFN exposure. We further report that the magnitude of these responses varied between different type I IFNs, whilst qualitatively different responses to type I IFN subtypes were not apparent. Taken together, we provide a rich resource mapping signalling responses and IFN-regulated genes in immune cells.HighlightsMass cytometry and scRNAseq analysis of human PBMCs stimulated with type I IFNsCell type-specific phosphorylation of STAT proteins and induction of ISGsDifferent type I IFNs induce qualitatively similar responses that vary in magnitudeIdentification of ten core ISGs, up-regulated by all cell types in response to all type I IFNsIn briefRigbyet al.provide a single-cell map of signalling and transcriptomic responses to type I IFNs inex vivostimulated human PBMCs. Different cell types responded in unique ways but differences between different type I IFNs were only quantitative. These rich datasets are available via an easy-to-use interactive interface (https://rehwinkellab.shinyapps.io/ifnresource/).Graphical abstract