bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying peripheral modulation of olfaction by trigeminal agonists
Authors: Federica Genovese , Jiang Xu , Marco Tizzano , Johannes Reisert 
Published: March 2023

AbstractIn the mammalian nose, two chemosensory systems, the trigeminal and the olfactory mediate the detection of volatile chemicals. Most odorants in fact are able to activate the trigeminal system, and vice versa, most trigeminal agonists activate the olfactory system as well. Although these two systems constitute two separate sensory modalities, trigeminal activation modulates the neural representation of an odor. The mechanisms behind the modulation of olfactory response by trigeminal activation are still poorly understood. In this study, we addressed this question by looking at the olfactory epithelium, where olfactory sensory neurons and trigeminal sensory fibers co-localize and where the olfactory signal is generated. We characterize the trigeminal activation in response to five different odorants by measuring intracellular Ca2+changes from primary cultures of trigeminal neurons (TGNs). We also measured responses from mice lacking TRPA1 and TRPV1 channels known to mediate some trigeminal responses. Next, we tested how trigeminal activation affects the olfactory response in the olfactory epithelium using electro-olfactogram (EOG) recordings from WT and TRPA1/V1-KO mice. The trigeminal modulation of the olfactory response was determined by measuring responses to the odorant, 2-phenylethanol (PEA), an odorant with little trigeminal potency after stimulation with a trigeminal agonist. Trigeminal agonists induced a decrease in the EOG response to PEA, which depended on the level of TRPA1 and TRPV1 activation induced by the trigeminal agonist. This suggests that trigeminal activation can alter odorant responses even at the earliest stage of the olfactory sensory transduction.Significance StatementMost odorants reaching the olfactory epithelium can simultaneously activate olfactory and trigeminal systems. Although these two systems constitute two separate sensory modalities, trigeminal activation can alter odor perception. Here, we analyzed the trigeminal activity induced by different odorants proposing an objective quantification of their trigeminal potency independent from human perception. We show that trigeminal activation by odorants reduces the olfactory response in the olfactory epithelium and that such modulation correlates with the trigeminal potency of the trigeminal agonist. These results show that the trigeminal system impacts the olfactory response from its earliest stage.
Post COVID-19 conditions in Children and Adolescents at 3 months following a Delta outbreak in Australia: a cohort study
Authors: Britton Philip N , Burrell Rebecca , Chapman Emily , Boyle Julia , Alexander Shirley , Belessis Yvonne , Dalby-Payne Jacqueline , Knight Katherine , Lau Christine , McMullan Brendan , Milne Bronwyn , Paull Marilyn , Nguyen Jonathan , Selvadurai Hiran , Dale Russell , Baillie Andrew 
Published: March 2023

AbstractBackgroundLong COVID remains incompletely understood in children and adolescents with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents.MethodsThe parents (or next of kin) of 11864 children and adolescents from a population catchment who had mandatory contact with Sydney Children’s Hospital Network facilities during acute SARS-CoV-2 infection (confirmed by PCR) were contacted by email or text message.Findings1731 (17.7%) responded to an online survey assessing symptoms, functional impairment. 203 of the responders (11.7%) gave answers that were consistent with continued symptoms and/or functional impairment and were flagged for clinical review. Of the 169 subsequently clinically reviewed, many had already recovered (n=63, 37.3%) or had a pre-existing condition exacerbated by COVID-19 (18, 10.7%); 64 (37.9%) were diagnosed with a Post COVID Condition (PCC). Of these, a minority we considered to have features compatible with the United Kingdom consensus cases definition for Long COVID (n=21).InterpretationDuring an outbreak of the Delta variant of SARS-CoV-2 an online questionnaire with clinical review follow-up provided evidence that a majority of children with COVID-19 had complete recovery at 12 weeks post infection, but those with persisting symptoms demonstrated a wide spectrum of severity and phenotype that comprises a likely significant burden that warrants attention for individuals and at a population level.FundingNew South Wales Health COVID-19 Emergency Response Priority Research Funding.
Identifying interaction interface betweenPseudomonasmajor biofilm forming functional amyloid FapC and disordered chaperone FapA during fibrillation deceleration
Authors: Byeon Chang-Hyeock , Saricayir Hakan , Hansen Kasper Holst , Jeffrey Jasper , Andreasen Maria , Akbey Ümit 
Published: March 2023

AbstractFunctional bacterial amyloids (FuBA) play a crucial role in the formation of biofilms, which are mediating chronic infections and contribute to antimicrobial resistance. This study focuses on the FapC protein fromPseudomonas, a major contributor to biofilm formation. We investigate the initial steps of FapC amyloid formation and the impact of the chaperone-like protein FapA on this process. Using solution NMR spectroscopy, we show that both FapC and FapA, which are part of the same biofilm-forming protein operon, are intrinsically disordered proteins (IDPs) in their soluble monomeric state. These SSPs were determined and compared to the Alphafold models. We further demonstrate that the IDP chaperone FapA interacts with FapC and significantly slows down the formation of FapC fibrils, while maintaining the fibril morphology unchanged. Our NMR titration experiments reveal that ∼18% of the resonances show FapA induced chemical shift perturbations (CPSs) which has not been previously observed, the largest being for A82, N201, C237, C240, A241 and G245 residues. These sites may suggest a specific interaction site and/or hotspots of fibrillation inhibition/control interface at the R1/L2 and L2/R3 transition areas and at the C-terminus of FapC. Remarkably, ∼90% of FapA NMR signals exhibit substantial CSPs upon titration with FapC. A temperature dependent effect of FapA was observed on FapC by ThT and NMR experiments. This study provides a detailed understanding of the interaction between the chaperone/chaperone-like FapA and the functional amyloid protein FapC, shedding light on the regulation and slowing down of amyloid formation. Our findings have important implications for the development of therapeutic strategies targeting biofilms and associated infections, leveraging these structural and mechanistic insights.
Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogenCryptococcus neoformans: a target for novel antifungals
Authors: Washington Erica J. , Zhou Ye , Hsu Allen L. , Petrovich Matthew , Tenor Jennifer L. , Toffaletti Dena L. , Guan Ziqiang , Perfect John R. , Borgnia Mario J. , Bartesaghi Alberto , Brennan Richard G. 
Published: March 2023

AbstractInvasive fungal diseases are a major threat to human health, resulting in more than 1.5 million annual deaths worldwide. The arsenal of antifungal therapeutics remains limited and is in dire need of novel drugs that target additional biosynthetic pathways that are absent from humans. One such pathway involves the biosynthesis of trehalose. Trehalose is a disaccharide that is required for pathogenic fungi to survive in their human hosts. In the first step of trehalose biosynthesis, trehalose-6-phosphate synthase (Tps1) converts UDP-glucose and glucose-6-phosphate to trehalose-6-phosphate. Here, we report the structures of full-lengthCryptococcus neoformansTps1 (CnTps1) in unliganded form and in complex with uridine diphosphate and glucose-6-phosphate. Comparison of these two structures reveals significant movement towards the catalytic pocket by the N-terminus upon ligand binding and identifies residues required for substrate-binding, as well as residues that stabilize the tetramer. Intriguingly, an intrinsically disordered domain (IDD), which is conserved amongst Cryptococcal species and closely related Basidiomycetes, extends from each subunit of the tetramer into the “solvent” but is not visible in density maps. We determined that the IDD is not required forC. neoformansTps1-dependent thermotolerance and osmotic stress survival. Studies with UDP-galactose highlight the exquisite substrate specificity of CnTps1.In toto, these studies expand our knowledge of trehalose biosynthesis inCryptococcusand highlight the potential of developing antifungal therapeutics that disrupt the synthesis of this disaccharide or the formation of a functional tetramer and the use of cryo-EM in the structural characterization of CnTps1-ligand/drug complexes.Significance StatementFungal infections are responsible for over a million deaths worldwide each year. Biosynthesis of a disaccharide, trehalose, is required for multiple pathogenic fungi to transition from the environment to the human host. Enzymes in the trehalose biosynthesis pathway are absent in humans and, therefore, are potentially significant targets for novel antifungal therapeutics. One enzyme in the trehalose biosynthesis is trehalose-6-phosphate synthase (Tps1). Here, we describe the cryo-electron microscopy structures of the CnTps1 homo-tetramer in the unliganded form and in complex with a substrate and a product. These structures and subsequent biochemical analysis reveal key details of substrate-binding residues and substrate specificity. These structures should facilitate structure-guided design of inhibitors against CnTps1.
Combining fusion of cells with CRISPR-Cas9 editing for the cloning of large DNA fragments or complete bacterial genomes in yeast
Authors: Guesdon Gabrielle , Gourgues Géraldine , Rideau Fabien , Ipoutcha Thomas , Manso-Silván Lucía , Jules Matthieu , Sirand-Pugnet Pascal , Blanchard Alain , Lartigue Carole 
Published: March 2023

AbstractThe genetic engineering of genome fragments larger than 100 kbp is challenging and requires both specific methods and cloning hosts. The yeastSaccharomyces cerevisiaeis considered as a host of choice for cloning and engineering whole or partial genomes from viruses, bacteria, and algae. Several methods are now available to perform these manipulations, each with its own limitations. In order to extend the range of in-yeast cloning strategies, a new approach combining two already described methods, the Fusion cloning and the CReasPy-Cloning, was developed. The CReasPy-Fusion method allows the simultaneous cloning and engineering of megabase-sized genomes in yeast by fusion of bacterial cells with yeast spheroplasts carrying the CRISPR-Cas9 system. With this new approach, we demonstrate the feasibility of cloning and editing whole genomes from severalMycoplasmaspecies belonging to different phylogenetic groups. We also show that CReasPy-Fusion allows the capture of large genome fragments with high efficacy, resulting in the successful cloning of selected loci in yeast. We finally identify bacterial nuclease encoding genes as barriers for CReasPy-Fusion by showing that their removal from the donor genome improves cloning efficacy.
Genomic surveillance reveals circulation of multiple variants and lineages of SARS-CoV-2 during COVID-19 pandemic in Indian city of Bengaluru
Authors: Sreenivas Darshan , Kumar Vinay , Kathirvel Kandasamy , Vadnala Rakesh Netha , Mishra Sachin , Shelar Bhagyashree , Marate Srilatha , CP Lakshminarayanan , K Sai Disha , Bhardwaj Manisha , Pandit Awadhesh , Mayor Satyajit , Ramakrishnan Uma , Notani Dimple 
Published: March 2023

AbstractGenomic surveillance in response to coronavirus disease (COVID-19) pandemic is crucial for tracking spread, identify variants of concern (VoCs) and understand the evolution of its etiological agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). India has experienced three waves of COVID-19 cases, which includes a deadly wave of COVID-19 that was driven by the Delta lineages (second/Delta wave) followed by another wave driven by the Omicron lineages (third/Omicron wave). These waves were particularly dramatic in the metropolitan cities due to high population density. We evaluated the prevalence, and mutational spectrum of SARS-CoV-2 variants/lineages in one such megapolis, Bengaluru city, across these three waves between October 2020 and June 2022. 15,134 SARS-CoV-2 samples were subjected to whole genome sequencing (WGS). Phylogenetic analysis revealed, SARS-CoV-2 variants in Bengaluru city belonged to 18 clades and 196 distinct lineages. As expected, the Delta lineages were the most dominant lineages during the second wave of COVID-19. The Omicron lineage BA.2 and its sublineages accounted for most of the COVID-19 cases in the third wave. Most number of amino acid changes were observed in spike protein. Among the 18 clades, majority of the mutations and least similarity at nucleotide sequence level with the reference genome were observed in Omicron clades.
Beta bursts correlate with synchronization of movements to rhythmic sounds
Authors: Chen Qiaoyu , McAllister Craig J. , Elliott Mark T. , Shapiro Kimron L. , Hanslmayr Simon 
Published: March 2023

AbstractAccumulating evidence indicates transient beta bursts play an important role in the representation of temporal information and prediction. However, the role of beta bursts in sensorimotor synchronization (SMS) involving active interactions between motor and sensory systems to synchronize predictive movements to periodic events remains unclear. To answer this question, 15 participants were invited to complete a finger-tapping task whilst high-density EEG (128 channels) was recorded. Participants tapped with their right index finger in synchrony with 1 Hz and 0.5 Hz tone trains. In line with previous findings, we found a negative mean asynchrony between tone and tap time, i.e., taps preceded tones for both tone frequencies (1 and 0.5 Hz). In the EEG data, beta bursts were detected and their timing in relationship with tapping and auditory tracking was examined. Results revealed that beta bursts tracked tapping and were modulated by the low frequency phase of the tone frequency (i.e., 1 Hz or 0.5 Hz). Importantly, the locking of beta bursts to the phase of auditory tracking correlated with the behavioural variance on a single trial level that occurred while tapping to the tones. These results demonstrate a critical role for an interplay between beta bursts and low frequency phase in coordinating rhythmic behaviour.
Cis-regulatory control of transcriptional timing and noise in response to estrogen
Authors: Ginley-Hidinger Matthew , Abewe Hosiana , Osborne Kyle , Richey Alexandra , Kitchen Noel , Mortenson Katelyn L. , Wissink Erin M. , Lis John , Zhang Xiaoyang , Gertz Jason 
Published: March 2023

AbstractCis-regulatory elements control transcription levels, temporal dynamics, and cell-cell variation or transcriptional noise. However, the combination of regulatory features that control these different attributes is not fully understood. Here, we used single cell RNA-seq during an estrogen treatment time course and machine learning to identify predictors of expression timing and noise. We find that genes with multiple active enhancers exhibit faster temporal responses. We verified this finding by showing that manipulation of enhancer activity changes the temporal response of estrogen target genes. Analysis of transcriptional noise uncovered a relationship between promoter and enhancer activity, with active promoters associated with low noise and active enhancers linked to high noise. Finally, we observed that co-expression across single cells is an emergent property associated with chromatin looping, timing, and noise. Overall, our results indicate a fundamental tradeoff between a gene’s ability to quickly respond to incoming signals and maintain low variation across cells.
Development of prefrontal corticostriatal connectivity in mice
Authors: Mesías Roxana E. , Zaki Yosif , Guevara Christopher A. , Friedman Lauren G. , Hussein Ayan , Therrien Karen , Magee Alexandra R. , Tzavaras Nikolaos , Valle Pamela Del , Baxter Mark G. , Huntley George W. , Benson Deanna L. 
Published: March 2023

SummaryRational decision making is grounded in learning to associate actions with outcomes, a process that depends on projections from prefrontal cortex to dorsomedial striatum. Symptoms associated with a variety of human pathological conditions ranging from schizophrenia and autism to Huntington’s and Parkinson’s disease point toward functional deficits in this projection, but its development is not well understood, making it difficult to investigate how perturbations in development of this circuitry could contribute to pathophysiology. We applied a novel strategy based on Hotspot Analysis to assess the developmental progression of anatomical positioning of prefrontal cortex to striatal projections. Corticostriatal axonal territories established at P7 expand in concert with striatal growth but remain largely unchanged in positioning through adulthood, indicating they are generated by directed, targeted growth and not modified extensively by postnatal experience. Consistent with these findings, corticostriatal synaptogenesis increased steadily from P7 to P56, with no evidence for widescale pruning. As corticostriatal synapse density increased over late postnatal ages, the strength of evoked PFC input onto dorsomedial striatal projection neurons also increased, but spontaneous glutamatergic synaptic activity was stable. Based on its pattern of expression, we asked whether the adhesion protein, Cdh8, influenced this progression. In mice lacking Cdh8 in PFC corticostriatal projection neurons, axon terminal fields in dorsal striatum shifted ventrally. Corticostriatal synaptogenesis was unimpeded, but spontaneous EPSC frequency declined and mice failed to learn to associate an action with an outcome. Collectively these findings show that corticostriatal axons grow to their target zone and are restrained from an early age, do not undergo postnatal synapse pruning as the most dominant models predict, and that a relatively modest shift in terminal arbor positioning and synapse function has an outsized, negative impact on corticostriatal-dependent behavior.
Deciphering the gut microbiome of grass carp through multi-omics approach
Authors: Li Ming , Liang Hui , Yang Hongwei , Ding Qianwen , Xia Rui , Chen Jie , Zhou Wenhao , Yang Yalin , Zhang Zhen , Yao Yuanyuan , Ran Chao , Zhou Zhigang 
Published: March 2023

AbstractBackgroundAquaculture plays an important role in global protein supplies and food security. The ban on antibiotics as feed additive proposes urgent need to develop alternatives. Gut microbiota plays important roles in the metabolism and immunity of fish, and has the potential to give rise to novel green inputs for fish culture. However, our understanding of fish gut microbiome is still lacking.ResultsWe identified 575,856 non-redundant genes by metagenomic sequencing of the intestinal content samples of grass carp. Taxonomic and functional annotation of the gene catalogue revealed specificity of the gut microbiome of grass carp compared with mammals. Co-occurrence analysis indicated exclusive relations between the genera belonging to Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes, suggesting two independent ecological groups of the microbiota. The association pattern of Proteobacteria with the gene expression modules of fish gut and liver was consistently opposite to that of Fusobacteria, Firmicutes and Bacteroidetes, implying differential functionality of Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes. Therefore, the two ecological groups were divided into two functional groups, i.e., Functional Group 1: Proteobacteria; Functional Group 2: Fusobacteria/Firmicutes/Bacteroidetes. Further analysis revealed that the two functional groups differ in genetic capacity for carbohydrate utilization, virulence factors and antibiotic resistance. Finally, we proposed that the ratio of “Functional Group 2/Functional Group 1” can be used as a biomarker that efficiently reflects the structural and functional characteristics of the microbiota of grass carp.ConclusionsThe gene catalogue is an important resource for investigating the gut microbiome of grass carp. Multi-omics analysis provides insights into functional implications of the main phyla that comprise the fish microbiota, and shed lights on targets for microbiota regulation.
How much storage precision can be lost: Guidance for near-lossless compression of untargeted metabolomics mass spectrometry data
Authors: Tong Junjie , Lu Miaoshan , Peng Bichen , An Shaowei , Wang Jinyin , Yu Changbin 
Published: March 2023

AbstractThe size of high-resolution mass spectrometry (HRMS) data has been increasing significantly. Several lossy compressors have been developed for higher compression rates. Currently, a comprehensive evaluation of what and how MS data (m/zand intensities) with precision losses would affect data processing (i.e., feature detection and compound identification) is absent.Here, we set an error threshold at 1% to assess the significance of the difference between two files in feature and compound detection results obtained from MZmine3. First, we examined that mzML files with bothm/zand intensity encoded in 32-bit precision appear to be a preferred combination via msConvert, which has smaller file size and minor variation with other combinations of storage precision (<0.13%). We then identified that the absolute error of 10−4form/zhad a feature detection error of 0.57% and compound detection error of 1.1%. For intensities, the relative error group of 2×10−2had an error of 4.65% for features and 0.98% for compounds, compared with precision-lossless files. Taken together, we provided a reasonable scene-accuracy proposal, with a maximum absolute error of 10−4form/zand a maximum relative error of 2×10−2for intensity. This guidance aimed to help researchers in improving lossy compression algorithms and minimizing the negative effects of precision losses on downstream data processing.
A rapid genome-wide analysis of isolated giant viruses only using MinION sequencing
Authors: Hikida Hiroyuki , Okazaki Yusuke , Zhang Ruixuan , Nguyen Thi Tuyen , Ogata Hiroyuki 
Published: March 2023

SummaryFollowing the discovery of Acanthamoeba polyphaga mimivirus, diverse giant viruses have been isolated. However, only a small fraction of these isolates has been completely sequenced, limiting our understanding of the genomic diversity of giant viruses. MinION is a portable and low-cost long-read sequencer that can be readily used in a laboratory. Although MinION provides highly error-prone reads that require correction through additional short-read sequencing, recent studies assembled high-quality microbial genomes only using MinION sequencing. Here, we evaluated the accuracy of MinION-only genome assemblies for giant viruses by re-sequencing a prototype marseillevirus. Assembled genomes presented over 99.98% identity to the reference genome with a few gaps, demonstrating a high accuracy of the MinION-only assembly. As a proof of concept, wede novoassembled five newly isolated viruses. Average nucleotide identities to their closest known relatives suggest that the isolates represent new species of marseillevirus, pithovirus, and mimivirus. Assembly of subsampled reads demonstrated that their taxonomy and genomic composition could be analyzed at the 50× sequencing coverage. We also identified a pithovirus gene whose homologues were detected only in metagenome-derived relatives. Collectively, we propose that MinION-only assembly is an effective approach to rapidly perform a genome-wide analysis of isolated giant viruses.