bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRPM5+microvillous tuft cells regulate neuroepithelial intrinsic olfactory stem cell proliferation
Authors: Ualiyeva Saltanat , Lemire Evan , Wong Caitlin , Boyd Amelia , Avilés Evelyn C. , Minichetti Dante G. , Perniss Alexander , Maxfield Alice , Roditi Rachel , Matsumoto Ichiro , Barrett Nora A. , Buchheit Kathleen M. , Laidlaw Tanya M. , Boyce Joshua A. , Bankova Lora G. , Haber Adam L 
Published: September 2022

AbstractThe olfactory neuroepithelium serves as a sensory organ for odors and is part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. A subset of these, microvillous cells (MVCs), are strategically positioned at the apical surface but their specific functions are still enigmatic and their relationship to the rest of the solitary chemosensory cell family is unclear. Here, we establish that the larger family of MVCs comprises tuft cells and ionocytes in both mice and humans. Olfactory TRPM5+tuft-MVCs share a core transcriptional profile with the chemosensory tuft family, prominently including the machinery for lipid mediator generation. Integrating analysis of the respiratory and olfactory epithelium, we define the unique receptor expression of TRPM5+tuft-MVC compared to the Gɑ-gustducin+respiratory tuft cells and characterize a new population of glandular DCLK1+tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we employed an integrated single-cell transcriptional and protein analysis. We defined a remodeling olfactory epithelial switch pathway with induction ofChil4and a distinct pathway of proliferation of the quiescent olfactory horizontal basal stem cell (HBC), both triggered in the absence of significant olfactory apoptosis. While theChil4pathway was dependent on STAT6 signaling and innate lymphocytes, neither were required for HBC proliferation. HBC proliferation was dependent on tuft-MVCs, establishing these specialized epithelial cells as both sensors for allergens and regulators of olfactory stem cell responses. Together our data provide high resolution characterization of the nasal tuft cell heterogeneity and uncover a novel mechanism by which TRPM5+tuft cells direct the olfactory mucosal response to allergens.One Sentence SummaryWe identify the enigmatic TRPM5+olfactory microvillous cells as tuft cells, and show their functional role as regulators of olfactory stem cell proliferation in response to environmental signals.
Probing Action Potential Generation and Timing under Multiplexed Basal Dendritic Computations Using Two-photon 3D Holographic Uncaging
Authors: Xiao Shulan , Yadav Saumitra , Jayant Krishna 
Published: September 2022

SUMMARYBasal dendrites of layer 5 cortical pyramidal neurons exhibit Na+ and NMDAR spikes, and are uniquely poised to influence somatic output. Nevertheless, due to technical limitations, how multibranch basal dendritic integration shapes action-potential output remains poorly mapped. Here, we combine 3D two-photon holographic transmitter-uncaging, whole-cell dynamic-clamp, and biophysical modeling, to reveal how synchronously activated synapses (distributed and clustered) across multiple basal dendritic branches impacts action-potential generation – under quiescent and in vivo like conditions. While dendritic Na+ spikes promote milli-second precision, distributed inputs and NMDAR spikes modulate firing rates via axo-somatic persistent sodium channel amplification. Action-potential precision, noise-enhanced responsiveness, and improved temporal resolution, were observed under high conductance states, revealing multiplexed dendritic control of somatic output amidst noisy membrane-voltage fluctuations and backpropagating spikes. Our results unveil a critical multibranch integration framework in which a delicate interplay between distributed synapses, clustered synapses, and axo-somatic subthreshold conductance’s, dictates somatic spike precision and gain.
BordetellaSpp. Utilize T3SS To Promote Secretion of IL1RA Leading to Long-Term Persistent Infections
Authors: Williams Tyler L. , Roan Connor , First Nicholas , Johnson Sarah , Gestal Monica C. 
Published: September 2022

ABSTRACTA common feature of pathogens is their ability to suppress host immune responses. Understanding the molecular mechanisms and the common pathways that bacteria utilize to block host immune signaling cascade might provide novel avenues for vaccine and therapeutic development. Preventable infectious diseases remain one of the major causes of morbidity and mortality worldwide and the current rise in antibiotic resistance is increasing this burden.Bordetellaspp. are respiratory pathogens that cause the long-term illness known as whooping cough.Bordetellainfections cause over 150,000 deaths each year, despite a vaccine being available. In our studies, we used the mouse pathogenB. bronchisepticato investigate the pneumonic stage of disease, which very well mimics the fatal disease caused byB. pertussis. In our previous work we discovered aB. bronchisepticamutant, RB50ΔbtrS, that clears rapidly from the lungs of mice and generates protective immunity that lasts for at least 15 months post-challenge. Combining the mouse immunological tools and both bacteria, the wildtype RB50 and mutant RB50ΔbtrS, which persists for up to 56 days and clears in 14-21 days, respectively, we investigated the mechanisms by which the wildtypeB. bronchisepticablocks host immune response to cause long term lung infection. Previous research indicated eosinophils as critical for rapid clearance of the mutant bacteria from the lungs.In vitroassays with eosinophils demonstrated that the RB50ΔbtrSmutant strain promotes the secretion of pro-inflammatory signals. In contrast, infection of eosinophils with RB50 promoted the secretion of anti-inflammatory signals such as IL1RA. Interestingly, IL1RA was also increased in the lungs of mice infected with the wildtype but not with the mutant RB50 strain. Infection with RB50ΔbscN, which lacks a functional type 3 secretion system (T3SS), was sufficient to prevent IL1RA induction suggesting that the bacterial effector responsible for IL1RA upregulation is a substrate of the T3SS. Supplementation with IL1RA after infection with RB50 or RB50ΔbtrSresulted in increased lung bacterial burden for both bacterial strains. However, more rapid clearance of RB50 was observed after infection of mice in which IL1RA was knocked out. Furthermore, anti-IL1RA antibody treatment promoted rapid clearance of not only RB50 but also the human pathogensB. pertussisandB. parapertussis. This suggests that IL1RA may be a promising therapeutic target to treat severe cases of whooping cough.Overall, this work demonstrates thatBordetellaspp. induces IL1RA expression to promote persistence using the T3SS. Since other bacteria have also been shown to target IL1RA, this may be a conserved bacterial mechanism to promote host-immune suppression.
Allelic variations and gene cluster modularity act as non-linear bottlenecks for cholera emergence
Authors: López-Pérez Mario , Balasubramanian Deepak , Crist Cole , Grant Trudy-Ann , Haro-Moreno Jose M. , Zaragoza-Solas Asier , Almagro-Moreno Salvador 
Published: September 2022

ABSTRACTCholera, an acute secretory diarrhea, is caused by strains from a phylogenetically confined group within theVibrio choleraespecies, the pandemic cholera group (PCG). To date, the molecular and evolutionary factors that enable the isolated emergence of toxigenicV. choleraefrom environmental populations remain mostly enigmatic. Comprehensive analyses of over 1,100V. choleraegenomes, including novel environmental isolates from this study, reveal that the species consists of four major clades and several minor ones. PCG belongs to a large clade located within a lineage shared with environmental strains, the pandemic cholera lineage. This hierarchical classification provided us with a framework to unravel the eco-evolutionary dynamics of the genetic determinants associated with the emergence of toxigenicV. cholerae. Our analyses indicate that this phenomenon is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. We determined that certain PCG-associated alleles are essential for successful colonization whereas others provide a non-linear competitive advantage, acting as a critical bottleneck that elucidates the isolated emergence of PCG. For instance, toxigenic strains encoding non-PCG alleles of a)tcpFor b) a sextuple allelic exchange mutant for genestcpA,toxT,VC0176,VC1791,rfbTandompU, lose their ability to colonize the intestine. Interestingly, these alleles do not play a role in the colonization of model environmental reservoirs. Our study uncovers the evolutionary roots of toxigenicV. choleraeand offers a tractable approach for investigating the emergence of pathogenic clones within an environmental population.SIGNIFICANCEThe underlying factors that lead to specific strains within a species to emerge as human pathogens remain mostly enigmatic. Toxigenic clones of the cholera agent,Vibrio cholerae, are encompassed within one phylogenomic clade, the pandemic cholera group (PCG). Here, we investigate the molecular and evolutionary factors that explain the confined nature of this group. Our analyses determined that the emergence of PCG is largely dependent on the acquisition of unique modular gene clusters and allelic variations that confer a competitive advantage during intestinal colonization. These allelic variations act as a critical bottleneck that elucidates the isolated emergence of PCG and provides a tractable blueprint for the study of the emergence of pathogenic clones within an environmental population.
Seasonal models reveal niche changes during invasion in Capsella bursa-pastoris
Authors: Brown Maya K. Wilson , Josephs Emily B. 
Published: September 2022

AbstractResearchers often use ecological niche models to predict where species might establish and persist under future or novel climate conditions. However, these predictive methods assume species have stable niches across time and space. Furthermore, ignoring the time of occurrence data can obscure important information about species reproduction and ultimately fitness. In this study, we generate full-year and monthly ecological niche models for Capsella bursa-pastoris to see if we can detect changes in the seasonal niche of the species after long-distance dispersal. We find full-year ecological niche models have low transferability across continents and there are continental differences in the climate conditions that influence the distribution of C. bursa-pastoris. Monthly models have greater predictive accuracy than full-year models in cooler seasons, but the inability of any model to predict summer occurrence in North America suggests a change in the seasonal niche from the native range to the non-native range. These results highlight the utility of ecological niche models at finer temporal scales in predicting species distributions and unmasking subtle patterns of evolution.
Thalamocortical boutons cluster by ON/OFF responses in mouse primary visual cortex
Authors: Tring Elaine , Ringach Dario L. 
Published: September 2022

AbstractIn higher mammals, the thalamic afferents to primary visual cortex cluster according to their responses to increases (ON) or decreases (OFF) in luminance. This feature of thalamocortical wiring is thought to create columnar, ON/OFF domains in V1. We have recently shown that mice also have ON/OFF cortical domains, but the organization of their thalamic afferents remains unknown. Here we measured the visual responses of thalamocortical boutons using two-photon imaging and found they also cluster in space according to ON/OFF responses. Moreover, fluctuations in the relative density of ON/OFF boutons mirrors fluctuations in the relative density of ON/OFF receptive field positions on the visual field. These findings indicate that there is a segregation of ON/OFF signals already present in the thalamic input, a result that may reflect the spatial organization of retinal ganglion cell mosaics themselves.New and NoteworthyNeurons in primary visual cortex cluster into ON and OFF domains, which have shown to be linked to the organization of receptive fields and cortical maps. Here we show that in the mouse, such clustering is already present in the thalamic input, suggesting that the cortical architecture is shaped by the periphery.
Cross-species predictive modeling reveals conserved drought responses between maize and sorghum
Authors: Pardo Jeremy , Wai Ching Man , Harman Max , Nguyen Annie , Kremling Karl A. , Romay Cinta , Lepak Nicholas , Bauerle Taryn L. , Buckler Edward S. , Thompson Addie M. , VanBuren Robert 
Published: September 2022

AbstractDrought tolerance is a highly complex trait controlled by numerous interconnected pathways with substantial variation within and across plant species. This complexity makes it difficult to distill individual genetic loci underlying tolerance, and to identify core or conserved drought responsive pathways. Here, we collected drought physiology and gene expression datasets across diverse genotypes of the C4 cereals sorghum and maize and searched for signatures defining water deficit responses. Differential gene expression identified few overlapping drought associated genes across sorghum genotypes, but using a predictive modeling approach, we found a shared core drought response across development, genotype, and stress severity. Our model had similar robustness when applied to datasets in maize, reflecting a conserved drought response between sorghum and maize. The top predictors are enriched in functions associated with various abiotic stress responsive pathways as well as core cellular functions. These conserved drought response genes were less likely to contain deleterious mutations than other gene sets, suggesting that core drought responsive genes are under evolutionary and functional constraints. Our findings support a broad evolutionary conservation of drought responses in C4 grasses regardless of innate stress tolerance, which could have important implications for developing climate resilient cereals.Significance StatementDrought is a complex and variable stress that is difficult to quantify and link to underlying mechanisms both within and across species. Here, we developed a predictive model to classify drought stress responses in sorghum and identify important features that are responsive to water deficit. Our model has high predictive accuracy across development, genotype, and stress severity, and the top features are enriched in genes related to classical stress responses and have functional and evolutionary conservation. We applied this sorghum trained model to maize, and observed similar predictive accuracy of drought responses, supporting transfer learning across plant species. Our findings suggest there are deeply conserved drought responses across C4 grasses that are unrelated to tolerance.
Resolution of structural variation in diverse mouse genomes reveals chromatin remodeling due to transposable elements
Authors: Ferraj Ardian , Audano Peter A. , Balachandran Parithi , Czechanski Anne , Flores Jacob I. , Radecki Alexander A. , Mosur Varun , Gordon David S. , Walawalkar Isha A. , Eichler Evan E. , Reinholdt Laura G. , Beck Christine R. 
Published: September 2022

SUMMARYDiverse inbred mouse strains are among the foremost models for biomedical research, yet genome characterization of many strains has been fundamentally lacking in comparison to human genomics research. In particular, the discovery and cataloging of structural variants is incomplete, limiting the discovery of potentially causative alleles for phenotypic variation across individuals. Here, we utilized long-read sequencing to resolve genome-wide structural variants (SVs, variants ≥ 50 bp) in 20 genetically distinct inbred mice. We report 413,758 site-specific SVs that affect 13% (356 Mbp) of the current mouse reference assembly, including 510 previously unannotated variants which alter coding sequences. We find that 39% of SVs are attributed to transposable element (TE) variation accounting for 75% of bases altered by SV. We then utilized this callset to investigate the impact of TE heterogeneity on mouse embryonic stem cells (mESCs), and find multiple TE classes that influence chromatin accessibility across loci. We also identify strain-specific transcription start sites originating in polymorphic TEs that modify gene expression. Our work provides the first long-read based analysis of mouse SVs and illustrates that previously unresolved TEs underlie epigenetic and transcriptome differences in mESCs.
Impact of phylogeny on structural contact inference from protein sequence data
Authors: Dietler Nicola , Lupo Umberto , Bitbol Anne-Florence 
Published: September 2022

AbstractLocal and global inference methods have been developed to infer structural contacts from multiple sequence alignments of homologous proteins. They rely on correlations in amino-acid usage at contacting sites. Because homologous proteins share a common ancestry, their sequences also feature phylogenetic correlations, which can impair contact inference. We investigate this effect by generating controlled synthetic data from a minimal model where the importance of contacts and of phylogeny can be tuned. We demonstrate that global inference methods, specifically Potts models, are more resilient to phylogenetic correlations than local methods, based on covariance or mutual information. This holds whether or not phylogenetic corrections are used, and may explain the success of global methods. We analyse the roles of selection strength and of phylogenetic relatedness. We show that sites that mutate early in the phylogeny yield false positive contacts. We consider natural data and realistic synthetic data, and our findings generalise to these cases. Our results highlight the impact of phylogeny on contact prediction from protein sequences and illustrate the interplay between the rich structure of biological data and inference.
Dopamine projections to the basolateral amygdala drive the encoding of identity-specific reward memories
Authors: Sias Ana C. , Jafar Yousif , Goodpaster Caitlin M. , Ramírez-Armenta Kathia , Wrenn Tyler M. , Griffin Nicholas K. , Patel Keshav , Lamparelli Alexander C. , Sharpe Melissa J. , Wassum Kate M. 
Published: September 2022

ABSTRACTTo make adaptive decisions, we build an internal model of the associative relationships in an environment and use it to make predictions and inferences about specific available outcomes. Detailed, identity-specific cue-reward memories are a core feature of such cognitive maps. Here we used fiber photometry, cell-type and pathway-specific optogenetic manipulation, Pavlovian cue-reward conditioning, and decision-making tests in male and female rats, to reveal that ventral tegmental area dopamine (VTADA) projections to the basolateral amygdala (BLA) drive the encoding of identity-specific cue-reward memories. Dopamine is released in the BLA during cue-reward pairing and VTADA→BLA activity is necessary and sufficient to link the identifying features of a reward to a predictive cue, but does not assign general incentive properties to the cue or mediate reinforcement. These data reveal a dopaminergic pathway for the learning that supports adaptive decision making and help explain how VTADAneurons achieve their emerging multifaceted role in learning.
Integrated Model of the Vertebrate Augmin Complex
Authors: Travis Sophie M , Mahon Brian P , Huang Wei , Ma Meisheng , Rale Michael J , Kraus Jodi S , Taylor Derek J , Zhang Rui , Petry Sabine 
Published: September 2022

ABSTRACTAccurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which exponentially amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but understanding how augmin promotes branching has been hindered by a lack of structural information about the complex. Here, we report an integrated model of vertebrate augmin, combining cryo-electron microscopy, advanced protein structural prediction, and the visualization of fused bulky tags via negative stain electron microscopy. This strategy allowed us to identify the location and orientation of each subunit within the structure. Evolutionary analysis of augmin’s structure reveals that it is highly conserved across diverse eukaryotes, and that augmin contains a previously-unidentified microtubule binding site. Moreover, we identify homology with the kinetochore-localized NDC80 complex. This new model of the augmin complex provides insight towards the mechanism and evolution of branching microtubule nucleation.
The genetic architecture of adaptation to leaf and root bacterial microbiota inArabidopsis thaliana
Authors: Roux Fabrice , Frachon Léa , Bartoli Claudia 
Published: September 2022

AbstractUnderstanding the role of host genome in modulating microbiota variation is a need to shed light into the holobiont theory and overcome the current limits on the description of host-microbiota interactions at the genomic and molecular levels. However, the host genetic architecture structuring microbiota is only partly described in plants. In addition, most association genetic studies on microbiota are often carried out outside the native habitats where the host evolve and the identification of signatures of local adaptation on the candidate genes has been overlooked. To fill these gaps and dissect the genetic architecture driving adaptive plant-microbiota interactions, we adopted a Genome-Environmental-Association (GEA) analysis on 141 whole-genome sequenced natural populations ofArabidopsis thalianacharacterizedin situfor their leaf and root bacterial communities and a large range of environmental descriptors (i.e. climate, soil and plant communities). Across 194 microbiota traits, a much higher fraction of among-population variance was explained by the host genetics than by ecology, with the plant neighborhood as the main ecological driver of microbiota variation. Importantly, the relative importance of host genetics and ecology expressed a phylogenetic signal at the family and genus level. In addition, the polygenic architecture of adaptation to bacterial communities was highly flexible between plant compartments and seasons. Relatedly, signatures of local adaptation were stronger on QTLs of the root microbiota in spring. Finally, we provide evidence that plant immunity, in particular theFLS2gene, is a major source of adaptive genetic variation structuring bacterial assemblages inA. thaliana.
Emergence and Persistent Dominance of Omicron BA.2.3.7 Variant in Community Outbreaks in Taiwan
Authors: Shao Pei-Lan , Tu Hsiao-Chen , Gong Yu-Nong , Shu Hung-Yu , Kirby Ralph , Hsu Li-Yun , Yeo Hui-Yee , Kuo Han-Yueh , Huang Yi-Chia , Lin Yung-Feng , Weng Hui-Ying , Wu Yueh-Lin , Chen Chien-Chih , Chen Tzen-Wen , Lee Kuo-Ming , Huang Chung-Guei , Shih Shin-Ru , Chen Wei J , Wu Chen-Chi , Yu Chong-Jen , Tsai Shih-Feng 
Published: September 2022

ABSTRACTSince April 2022, waves of Omicron cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we have analyzed 2405 PCR-positive swab samples from 2339 individuals and identified the Omicron BA.2.3.7 variant as a major lineage within the recent community outbreak in Taiwan.