bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety Recommendations for Temporal Interference Stimulation in the Brain
Authors: Cassarà Antonino M. , Newton Taylor H. , Zhuang Katie , Regel Sabine J. , Achermann Peter , Kuster Niels , Neufeld Esra 
Published: December 2022

AbstractTemporal interference stimulation (TIS) is a new form of transcranial electrical stimulation (tES) that has been proposed as a method for targeted, non-invasive stimulation of deep brain structures. While TIS holds promise for a variety of clinical and non-clinical applications, little data is yet available regarding its effects in humans. To inform the design and approval of experiments involving TIS, researchers require quantitative guidance regarding exposure limits and other safety concerns. To this end, we sought to delineate a safe range of exposure parameters (voltages and currents applied via external scalp electrodes) for TIS in humans through comparisons with well-established but related brain stimulation modalities. Specifically, we surveyed the literature for adverse events (AEs) associated with transcranial alternating/direct current stimulation (tACS/tDCS), deep brain stimulation (DBS), and TIS to establish known boundaries for safe operating conditions. Drawing on the biophysical mechanisms associated with the identified AEs, we determined appropriate exposure metrics for each stimulation modality. Using these metrics, we conducted anin silicocomparison of various exposure scenarios for tACS, DBS, and TIS using multiphysics simulations in an anatomically detailed head model with realistic current strengths. By matching stimulation scenarios in terms of biophysical impact, we inferred the frequency-dependent TIS stimulation parameters that resulted in exposure magnitudes known to be safe for tACS and DBS. Based on the results of our simulations and existing knowledge regarding tES and DBS safety, we propose frequency-dependent thresholds below which TIS voltages and currents are unlikely to pose a risk to humans. Safety-related data from ongoing and future human studies are required to verify and refine the thresholds proposed here.
Tools for connectomic reconstruction and analysis of a femaleDrosophilaventral nerve cord
Authors: Azevedo Anthony , Lesser Ellen , Phelps Jasper S. , Mark Brandon , Elabbady Leila , Kuroda Sumiya , Sustar Anne , Moussa Anthony , Kandelwal Avinash , Dallmann Chris J. , Agrawal Sweta , Lee Su-Yee J. , Pratt Brandon , Cook Andrew , Skutt-Kakaria Kyobi , Gerhard Stephan , Lu Ran , Kemnitz Nico , Lee Kisuk , Halageri Akhilesh , Castro Manuel , Ih Dodam , Gager Jay , Tammam Marwan , Dorkenwald Sven , Collman Forrest , Schneider-Mizell Casey , Brittain Derrick , Jordan Chris S. , Dickinson Michael , Pacureanu Alexandra , Seung H. Sebastian , Macrina Thomas , Lee Wei-Chung Allen , Tuthill John C. 
Published: December 2022

SummaryLike the vertebrate spinal cord, the insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we apply automated tools for electron microscopy volume alignment, neuron segmentation, and synapse prediction toward creating a connectome of an adult femaleDrosophilaVNC. To interpret a connectome, it is crucial to know its relationship with the rest of the body. We therefore mapped the muscle targets of leg and wing motor neurons in the connectome by comparing their morphology to genetic driver lines, dye fills, and X-ray nano-tomography of the fly leg and wing. Knowing the outputs of the connectome allowed us to identify neural circuits that coordinate the wings and legs during escape takeoff. We provide the reconstruction of VNC circuits and motor neuron atlas, along with tools for programmatic and interactive access, as community resources to support experimental and theoretical studies of how the fly nervous system controls behavior.
Diversity and pathobiology of an ilarvirus unexpectedly detected in diverse host plants and in global sequencing data
Authors: Rivarez Mark Paul Selda , Faure Chantal , Svanella-Dumas Laurence , Pecman Anja , Tušek-Žnidaric Magda , Schönegger Deborah , De Jonghe Kris , Blouin Arnaud , Massart Sebastien , Ravnikar Maja , Kutnjak Denis , Marais Armelle , Candresse Thierry 
Published: December 2022

ABSTRACTHigh-throughput sequencing (HTS) and sequence mining tools revolutionized virus detection and discovery in recent years and implementing them with classical plant virology techniques results to a powerful approach to characterize viruses. An example of a virus discovered through HTS is Solanum nigrum ilarvirus 1 (SnIV1) (familyBromoviridae), which was recently reported in various solanaceous plants from France, Slovenia, Greece, and South Africa. It was likewise detected in grapevines (Vitaceae) and severalFabaceaeandRosaceaeplant species. Such a very diverse host association is atypical for ilarviruses, thus warranted further investigation. In this study, modern and classical virological tools were combined to accelerate the characterization of SnIV1. Through HTS-based virome surveys, mining of sequence read archive datasets, and literature search, SnIV1 was further identified from diverse plant and non-plant sources globally. SnIV1 isolates showed relatively low variability compared to other phylogenetically related ilarviruses. Phylogenetic analyses showed a distinct basal clade of isolates from Europe, while the rest formed clades of mixed geographic origin. Furthermore, systemic infection of SnIV1 inSolanum villosumand its mechanical and graft transmissibility to solanaceous species were demonstrated. Near identical SnIV1 genomes from the inoculum (S. villosum) and inoculatedNicotiana benthamianawere sequenced, thus partially fulfilling Koch’s postulates. SnIV1 was shown to be seed-transmitted and potentially pollen-borne, has spherical virions, and possibly induces histopathological changes in infectedN. benthamianaleaf tissues. Overall, this study provided information to better understand the diversity, distribution, and pathobiology of SnIV1, but whether it could emerge as a destructive pathogen remains uncertain.FundingEU Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Network (H2020 MSCA-ITN) project no. GA 813542Administration of the Republic of Slovenia for Food Safety, Veterinary Sector and Plant Protection and Slovenian Research Agency (ARRS) funding no. P4-0165, P4-0407, J4-4553Balik Scientist Program (Republic Act 11035) of the Department of Science and Technology– Philippine Council for Agriculture, Aquatic, and Natural Resources Research and Development (DOST–PCAARRD), Republic of the PhilippinesThe Belgian FPS Health Food Chain Safety and Environment under Project RT18/3 SEVIPLANT
In vitroandin vivoinfection models reveal connection between periplasmic protease Prc and alternative peptidoglycan synthase PBP3SALinSalmonella entericaserovar Typhimurium
Authors: Vestö Kim , Frederiksen Rikki F. , Snygg Iina , Fahlgren Anna , Fällman Maria , Rhen Mikael 
Published: December 2022

AbstractA hallmark in salmonellosis is the ability of the bacteria to proliferate within host cells. Most notably,Salmonellaproliferates within professional phagocytes in a vacuolar compartment. During proliferationSalmonellahas to build new cell wall, but how this is regulated within the intraphagosomal niche is not known. Here we show that genetically inactivating the periplasmic protease Prc, involved in cleaving peptidoglycan-processing enzymes, results in decreased fitness in macrophage-like RAW264.7 cells and in BALB/c mice, and in a decreased tolerance to redox stress. All theseprcmutant phenotypes were conditional depending onpbp3sal, a recently defined paralogue forftslcoding for the essential penicillin binding protein 3. These phenotypic connections between Prc and PBP3SALadds to the phenotypes governed by Prc, and possibly adds PBP3SALto the pool of target proteins involved in cell wall homeostasis that are regulated by Prc.
Characterizing endogenous delta oscillations in human MEG
Authors: Gunasekaran Harish , Azizi Leila , van Wassenhove Virginie , Herbst Sophie K. 
Published: December 2022

AbstractRhythmic activity in the delta frequency range (0.5 – 3 Hz) is a prominent feature of brain dynamics. Here, we examined whether spontaneous delta oscillations, as found in invasive recordings in awake animals, can be observed in non-invasive recordings pewwrformed in humans with magnetoencephalography (MEG). In humans, delta activity is commonly reported when processing rhythmic sensory inputs, with direct relationships to behaviour. However, rhythmic brain dynamics observed during rhythmic sensory stimulation cannot be interpreted as anendogenousoscillation. To test for endogenous delta oscillations we analysed human MEG data during rest. For comparison, we additionally analysed two conditions in which participants engaged in spontaneous finger tapping and silent counting, arguing that internally rhythmic behaviours could incite an otherwise silent neural oscillator. A novel set of analysis steps allowed us to show narrow spectral peaks in the delta frequency range in rest, and during overt and covert rhythmic activity. Additional analyses in the time domain revealed that only the resting state condition warranted an interpretation of these peaks as endogenously periodic neural dynamics. In sum, this work shows that using advanced signal processing techniques, it is possible to observe endogenous delta oscillations in non-invasive recordings of human brain dynamics.
Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T-cell recognition epitopes
Authors: Muik Alexander , Lui Bonny Gaby , Diao Huitian , Fu Yunguan , Bacher Maren , Toker Aras , Grosser Jessica , Ozhelvaci Orkun , Grikscheit Katharina , Hoehl Sebastian , Kohmer Niko , Lustig Yaniv , Regev-Yochay Gili , Ciesek Sandra , Beguir Karim , Poran Asaf , Türeci Özlem , Sahin Ugur 
Published: December 2022

AbstractThe continued evolution of the SARS-CoV-2 Omicron variant has led to the emergence of numerous sublineages with different patterns of evasion from neutralizing antibodies. We investigated neutralizing activity in immune sera from individuals vaccinated with SARS-CoV-2 wild-type spike (S) glycoprotein-based COVID-19 mRNA vaccines after subsequent breakthrough infection with Omicron BA.1, BA.2, or BA.4/BA.5 to study antibody responses against sublineages of high relevance. We report that exposure of vaccinated individuals to infections with Omicron sublineages, and especially with BA.4/BA.5, results in a boost of Omicron BA.4.6, BF.7, BQ.1.1, and BA.2.75 neutralization, but does not efficiently boost neutralization of sublineages BA.2.75.2 and XBB. Accordingly, we found inin silicoanalyses that with occurrence of the Omicron lineage a large portion of neutralizing B-cell epitopes were lost, and that in Omicron BA.2.75.2 and XBB less than 12% of the wild-type strain epitopes are conserved. In contrast, HLA class I and class II presented T-cell epitopes in the S glycoprotein were highly conserved across the entire evolution of SARS-CoV-2 including Alpha, Beta, and Delta and Omicron sublineages, suggesting that CD8+and CD4+T-cell recognition of Omicron BQ.1.1, BA.2.75.2, and XBB may be largely intact. Our study suggests that while some Omicron sublineages effectively evade B-cell immunity by altering neutralizing antibody epitopes, S protein-specific T-cell immunity, due to the very nature of the polymorphic cell-mediated immune, response is likely to remain unimpacted and may continue to contribute to prevention or limitation of severe COVID-19 manifestation.
A schema for digitized surface swab site metadata in open-source DNA sequence databases
Authors: Feng Barry , Daeschel Devin , Dooley Damion , Griffiths Emma , Allard Marc , Timme Ruth , Chen Yi , Snyder Abigail B. 
Published: December 2022

ABSTRACTLarge, open-source DNA sequence databases have been generated, in part, through the collection of microbial pathogens from swabbing surfaces in built environments. Analyzing these data in aggregate through public health surveillance requires digitization of the complex, domain-specific metadata associated with swab site locations. However, the swab site location information is currently collected in a single, free-text “isolation source” field promoting generation of poorly detailed descriptions with varying word order, granularity, and linguistic errors, making automation difficult and reducing machine-actionability. We assessed 1,498 free-text swab site descriptions generated during routine foodborne pathogen surveillance. The lexicon of free-text metadata was evaluated to determine the informational facets and quantity of unique terms used by data collectors. Open Biological Ontologies (OBO) foundry libraries were used to develop hierarchical vocabularies connected with logical relationships to describe swab site locations. Five informational facets described by 338 unique terms were identified via content analysis. Term hierarchy facets were developed as were statements (called axioms) about how entities within these five domains were related. The schema developed through this study has been integrated into a publicly available pathogen metadata standard, facilitating ongoing surveillance and investigations. The One Health Enteric Package is available at NCBI BioSample beginning in 2022. Collective use of metadata standards increases the interoperability of DNA sequence databases, enabling large-scale approaches to data sharing, artificial intelligence, and big-data solutions to food safety.IMPORTANCERegular analysis of whole genome sequence data in collections such as NCBI’s Pathogen Detection Database is used by many public health organizations to detect outbreaks of infectious disease. However, isolate metadata in these databases are often incomplete and poor quality. These complex raw metadata must often be re-organized and manually formatted for use in aggregate analysis. These processes are inefficient and time-consuming, increasing the interpretative labor needed by public health groups to extract actionable information. Future use of open genomic epidemiology networks will be supported through the development of an internationally applicable vocabulary system to describe swab site locations.
Reconstructing Spatio-Temporal Trajectories of Visual Object Memories in the Human Brain
Authors: Lifanov Julia , Griffiths Benjamin J. , Linde-Domingo Juan , Ferreira Catarina S. , Wilson Martin , Mayhew Stephen D. , Charest Ian , Wimber Maria 
Published: December 2022

AbstractOur understanding of how information unfolds when we recall events from memory remains limited. In this study, we investigate whether the reconstruction of visual object memories follows a backward trajectory along the ventral visual stream with respect to perception, such that their neural feature representations are gradually reinstated from late areas close to the hippocampus backwards to lower-level sensory areas. We use multivariate analyses of fMRI activation patterns to map the constituent features of the object memories onto the brain during retrieval, and EEG-fMRI fusion to track the temporal evolution of the reactivated patterns. Participants studied new associations between verbs and randomly paired object images in an encoding phase, and subsequently recalled the objects when presented with the corresponding verb cue. Decoding reactivated memory features from fMRI activity revealed that retrieval patterns were dominated by conceptual features, represented in comparatively late visual and parietal areas. Representational-similarity-based fusion then allowed us to map the EEG patterns that emerged at each given time point of a trial onto the spatially resolved fMRI patterns. This fusion suggests that memory reconstruction proceeds backwards along the ventral visual stream from anterior fronto-temporal to posterior occipital and parietal regions, in line with a semantic-to-perceptual gradient. A linear regression on the peak time points of reactivated brain regions statistically confirms that the temporal progression is reversed with respect to encoding. Together, the results shed light onto the spatio-temporal trajectories along which memories are reconstructed during associative retrieval, and which features of an image are reconstructed when in time and where in the brain.
Domain loss enabled evolution of novel functions in a gene superfamily
Authors: Koludarov Ivan , Senoner Tobias , Jackson Timothy N. W. , Dashevsky Daniel , Heinzinger Michael , Aird Steven D. , Rost Burkhard 
Published: December 2022

AbstractThree-finger toxins (3FTxs) are a functionally diverse family of toxins, apparently unique to venoms of caenophidian snakes. Although the ancestral function of 3FTxs is antagonism of nicotinic acetylcholine receptors (nAChR), redundancy conferred by accumulation of duplicate genes has facilitated extensive neofunctionalization, such that derived members of the family interact with a range of targets. 3FTxs are members of the Ly6/uPAR family, but their non-toxin ancestor remains unknown. Combining traditional phylogenetic approaches, manual synteny analysis, and cutting-edge machine learning techniques (includingAlphaFold2andProtT5), we have reconstructed a detailed evolutionary history of 3FTxs. We identify their immediate ancestor as a non-secretory Ly6, unique to squamate reptiles, and propose that changes in molecular ecology resulting from loss of a membrane-anchoring domain (MaD) and changes in gene expression, paved the way for evolution of one of the most important families of snake toxins.
Red Algae-Derived Mineral Intervention to Counter Pro-inflammatory Activity in Human Colon Organoids
Authors: Varani James , McClintock Shannon D , Nadeem Daniyal M , Harber Isabelle , Zeidan Dania , Aslam Muhammad N 
Published: December 2022

ABSTRACTHuman colon organoids were maintained in culture medium alone or exposed to lipopolysaccharide with a combination of three pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β and interferon-γ [LPS-cytokines]) to mimic the environment in the inflamed colon. Untreated organoids and those exposed to LPS-cytokines were concomitantly treated with a multimineral product that has previously been shown to improve barrier structure/function. The organoids were subjected to proteomic analysis to obtain a broad view of the protein changes induced by these interventions. In parallel, confocal fluorescence microscopy and trans-epithelial electrical resistance measurements were used to assess barrier structure/function. The LPS-cytokines altered expression of multiple proteins that influence innate immunity and promote inflammation. Most of these were unaffected by the multi-mineral intervention, though a subset of inflammation-related proteins including fibrinogen-β and -γ chains, phospholipase A2 and SPARC was down-regulated in the presence of the multi-mineral intervention; another subset of proteins with anti-inflammatory, antioxidant or antimicrobial activity was up-regulated by multi-mineral treatment. When used alone, the multi-mineral intervention strongly up-regulated proteins that contribute to barrier formation and tissue strength. Concomitant treatment with LPS-cytokines did not inhibit barrier formation in response to the multimineral intervention. Altogether, the findings suggest that mineral intervention may provide a novel approach to combating inflammation in the colon by improving barrier structure/function as well as by directly altering expression of pro-inflammatory proteins.
Molecular evolution and structural analyses of spike protein COVID-19 variants in Negeri Sembilan of peninsular Malaysia
Authors: Mat-Sharani Shuhaila , A/L Kumareahsan Danish , Ismail Ismatul Nurul Asyikin , Mohamad Jamali Muhamad Arif , Azmi Liyana 
Published: December 2022

AbstractThe sharing of COVID-19 sequences worldwide has allowed for comprehensive and real-time analyses of COVID-19 genomic diversity at regional levels. Temporal distribution of COVID-19 variants and lineages enables better infection control, surveillance, and facilitates policy making for public health. 417 sequences extracted from all COVID-19 cases in Negeri Sembilan of peninsular Malaysia from July 2021 until May 2022 were used for this study. Phylogenomics revealed a total of 20 circulating lineages, of which seven are still circulating. The majority (60.4%) of viruses in Negeri Sembilan are of GRA lineage with strong representation from the Malaysian lineage BA.1.1 (24.7%). A time series analysis showed a change in the dominating circulating lineage from AY.79 to BA.1.1, which correlated to the relaxing of lockdowns implemented by the Malaysian government. Several Malaysian sub-lineages (BA.2.40.1, BA.2.57 and BA.2.9) have emerged from April 2022 onwards. Evolutionary mutations of the sub-lineages also gave rise to novel single nucleotide polymorphisms (SNPs) in the spike proteins. Out of the 70 SNPs isolated from all samples,in silicoprediction revealed five novel SNPs that could cause functional defects to the spike protein, which are S221L, L226S, V826L, C1240F and C1243F. Structural modelling of the V826L showed that the L826 possibly confers an increase in protein flexibility within the S2 region of S protein, which supports ourin-silicopredictions.
Wetting of junctional condensates along the apical interface promotes tight junction belt formation
Authors: Pombo-García Karina , Martin-Lemaitre Cecilie , Honigmann Alf 
Published: December 2022

ABSTRACTBiomolecular condensates enable cell compartmentalization by acting as membrane-less organelles1. How cells control the interactions of condensates with other cellular structures such as membranes to drive morphological transitions remains poorly understood. Here, we studied formation of tight junctions, which initially assemble as condensates that over time elongate around the membrane cell perimeter to form a closed junctional barrier2. We discovered that the elongation of junctional condensates is driven by a physical wetting process around the apical membrane interface. Using temporal proximity proteomics in combination with live and super-resolution imaging, we found that wetting is mediated by the apical protein PATJ, which promotes adhesion of condensates to the apical membrane resulting in an interface formation and linear spreading into a closed belt. Using PATJ mutations we show that apical adhesion of junctional condensates is necessary and sufficient for stable tight junction belt formation. Our results demonstrate how cells exploit the collective biophysical properties of protein condensates and membrane interfaces to shape mesoscale structures.