bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022
Authors: Klaassen Fayette , Chitwood Melanie H. , Cohen Ted , Pitzer Virginia E. , Russi Marcus , Swartwood Nicole A. , Salomon Joshua A. , Menzies Nicolas A. 
Published: November 2022

AbstractImportanceWhile a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021 – February 2022, the subsequent evolution of population immunity against SARS-CoV-2 Omicron variants reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations.ObjectiveTo estimate changes in population immunity against infection and severe disease due to circulating SARS-CoV-2 Omicron variants in the United States from December 2021 to November 2022, and to quantify the protection against a potential 2022-2023 winter SARS-CoV-2 wave.Design, setting, participantsBayesian evidence synthesis of reported COVID-19 data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, using a mathematical model of COVID-19 natural history.Main Outcomes and MeasuresPopulation immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week.ResultsBy November 9, 2022, 94% (95% CrI, 79%–99%) of the US population were estimated to have been infected by SARS-CoV-2 at least once. Combined with vaccination, 97% (95%–99%) were estimated to have some prior immunological exposure to SARS-CoV-2. Between December 1, 2021 and November 9, 2022, protection against a new Omicron infection rose from 22% (21%–23%) to 63% (51%–75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%–64%) to 89% (83%–92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4–7.2) and protection against severe disease by 1.1 percentage points (1.0–1.5).Conclusions and RelevanceEffective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave.Key pointsQuestionHow did population immunity against SARS-CoV-2 infection and subsequent severe disease change between December 2021, and November 2022?FindingsOn November 9, 2022, the protection against a SARS-CoV-2 infection with the Omicron variant was estimated to be 63% (51%–75%) in the US, and the protection against severe disease was 89% (83%–92%).MeaningAs most of the newly acquired immunity has been accumulated in the December 2021-February 2022 Omicron wave, risk of reinfection and subsequent severe disease remains present at the beginning of the 2022-2023 winter, despite high levels of protection.
Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C)
Authors: Perez Maria A. , Hsiao Hui-Mien , Chen Xuemin , Kunkel Amber , Baida Nadine , Hussaini Laila , Lu Austin T. , Kao Carol M. , Laham Federico R. , Hunstad David A. , Beltran Yajira , Hammett Teresa A. , Godfred-Cato Shana , Chahroudi Ann , Anderson Evan J. , Belay Ermias , Rostad Christina A. 
Published: November 2022

ABSTRACTUnderstanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled five children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies waned following acute MIS-C, but were significantly boosted with vaccination and maintained for at least 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n=6) and children with history of MIS-C (n=5) or COVID-19 (n=5). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were reduced to the Omicron variant. Vaccination after MIS-C or COVID-19 (hybrid immunity) conferred advantage in generating pseudovirus neutralizing and functional ADCC antibodies to Omicron.
Angle-dependence and auxin asymmetry: towards the formulation of a universal theory of root gravitropism
Authors: Sageman-Furnas K. , Del Bianco M. , Friml J. , Wolverton C. , Kepinski S. 
Published: November 2022

AbstractGravitropism has been conceptualized through three main theories: the starch-statolith model for sensing, the Cholodny-Went model of growth control via auxin asymmetry, and the law of angle-dependence for behavior, in which the magnitude of gravitropic response increases with displacement from the vertical. While experimental data show that the generation of both Cholodny-Went-type auxin gradients and angle-dependent behavior requires statolith sedimentation, a link between auxin asymmetry and angle-dependence has not been demonstrated. Here, we use large scale reorientation assays of Arabidopsis roots, epidermal length measurements, and confocal microscopy to quantify auxin distribution and PIN localization during graviresponse. We show angle-dependence in auxin asymmetry and growth response, even at low stimulation angles. As such, our work integrates the three theories sensing, signal transduction and behavior into a single unified model of gravitropism and provides an important framework for exploring major outstanding questions in the field.
A shared neural code for the physics of actions and object events
Authors: Akbiyik Seda , Caramazza Alfonso , Wurm Moritz 
Published: November 2022

ABSTRACTObserving others’ actions recruits frontoparietal and posterior temporal brain regions – also called the action observation network. It is typically assumed that these regions support recognizing actions of animate entities (e.g., person jumping over a box). However, objects can also participate in events with rich meaning and structure (e.g., ball bouncing over a box). So far, it has not been clarified which brain regions encode information specific to goal-directed actions or more general information that also defines object events. Here, we show a shared neural code for visually presented actions and object events throughout the action observation network. We argue that this neural representation captures the structure and physics of events regardless of animacy. We find that lateral occipitotemporal cortex encodes information about events that is also invariant to stimulus modality. Our results shed light onto the representational profiles of posterior temporal and frontoparietal cortices, and their roles in encoding event information.
Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss
Authors: Castor-Macias Jesus A. , Larouche Jacqueline A. , Wallace Emily C. , Spence Bonnie D. , Eames Alec , Yang Benjamin A. , Davis Carol , Brooks Susan V. , Maddipati Krishna Rao , Markworth James F. , Aguilar Carlos A. 
Published: November 2022

AbstractThe acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and improved myogenesis, leading to enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.
GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data
Authors: Ajaib Shoaib , Lodha Disha , Pollock Steven , Hemmings Gemma , Finetti Martina A. , Gusnanto Arief , Chakrabarty Aruna , Ismail Azzam , Wilson Erica , Varn Frederick S , Hunter Bethany , Filby Andrew , Brockman Asa A. , McDonald David , Verhaak Roel GW , Ihrie Rebecca A. , Stead Lucy F. 
Published: November 2022

AbstractThe biological and clinical impact of neoplastic and immune cell type ratios in the glioblastoma (GBM) tumour microenvironment is being realised. Characterising and quantifying cell types within GBMs at scale will facilitate a better understanding of the association between the cellular landscape and tumour phenotypes or clinical correlates. This study aimed to develop a tool that can deconvolute immune and neoplastic cells within the GBM tumour microenvironment from bulk RNA sequencing data. We developed an IDH wild-type (IDHwt) GBM specific single immune cell reference dataset, from four independent studies, consisting of B cells, T cells, NK cells, microglia, tumour associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type dataset consisting of astrocyte-like, oligodendrocyte- and neuronal-progenitor like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We then applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumours, in parallel with these tools to determine which performed best. Marker based gene expression deconvolution using GBM tissue specific markers, which we have packaged as GBMdeconvoluteR, gave the most accurate results. The correlation between immune cell quantification by IMC and by GBMdeconvoluteR for primary IDHwt GBM samples was 0.52 (Pearson’s P=7.8×10−3) and between neoplastic cell quantification by IMC and by GBMdeconvoluteR was 0.75 (Pearson’s P=1.2×10−3). We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas (TCGA) and were able to recapitulate recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we were able to expand upon this to show that these associations are stronger in patients with worse prognosis. GBMdeconvoluteR is accessible online athttps://gbmdeconvoluter.leeds.ac.uk.Key pointsGBMdeconvoluteR is a glioblastoma-specific cellular deconvolution tool. When applied to bulk GBM RNAseq data, it accurately quantifies the neoplastic and immune cells in that tumour. It is available online athttps://gbmdeconvoluter.leeds.ac.uk
Evolution of the SARS-CoV-2 mutational spectrum
Authors: Bloom Jesse D , Beichman Annabel C , Neher Richard A , Harris Kelley 
Published: November 2022

AbstractSARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single nucleotide mutations at four-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly two-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al (2022). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors—although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution, and suggests that human SARS-CoV-2 may be trending towards a mutation spectrum more similar to that of other animal sarbecoviruses.
TheRuminococcus bromiiamylosome protein Sas6 binds single and double helical α-glucan structures in starch
Authors: Photenhauer Amanda L. , Cerqueira Filipe M. , Villafuerte-Vega Rosendo , Armbruster Krista M. , Mareček Filip , Chen Tiantian , Wawrzak Zdzislaw , Hopkins Jesse B. , Vander Kooi Craig W. , Janeček Štefan , Ruotolo Brandon T. , Koropatkin Nicole M. 
Published: November 2022

AbstractResistant starch is a prebiotic with breakdown by gut bacteria requiring the action of specialized amylases and starch-binding proteins. The human gut symbiontRuminococcus bromiiexpresses granular starch-binding protein Sas6 (Starch Adherence System member 6) that consists of two starch-specific carbohydrate binding modules from family 26 (RbCBM26) and family 74 (RbCBM74). Here we present the crystal structures of Sas6 andRbCBM74 with a double helical dimer of maltodecaose bound along an extended surface groove. Binding data combined with native mass spectrometry suggest that RbCBM26 binds short maltooligosaccharides while RbCBM74 can bind single and double helical α-glucans. Our results support a model by which RbCBM74 and RbCBM26 bind neighboring α-glucan chains at the granule surface. CBM74s are conserved among starch granule-degrading bacteria and our work provides molecular insight into how this structure is accommodated by select gut species.
Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
Authors: Francisco Junior Ronaldo da Silva , Temerozo Jairo R. , Ferreira Cristina dos Santos , Martins Yasmmin , Souza Thiago Moreno L. , Medina-Acosta Enrique , de Vasconcelos Ana Tereza Ribeiro 
Published: November 2022

AbstractCell entry of SARS-CoV-2 causes genome-wide disruption of the transcriptional profiles of genes and biological pathways involved in the pathogenesis of COVID-19. Expression allelic imbalance is characterized by a deviation from the Mendelian expected 1:1 expression ratio and is an important source of allele-specific heterogeneity. Expression allelic imbalance can be measured by allele-specific expression analysis (ASE) across heterozygous informative expressed single nucleotide variants (eSNVs). ASE reflects many regulatory biological phenomena that can be assessed by combining genome and transcriptome information. ASE contributes to the interindividual variability associated with disease. We aim to estimate the transcriptome-wide impact of SARS-CoV-2 infection by analyzing eSNVs. We compared ASE profiles in the human lung cell lines Calu-3, A459, and H522 before and after infection with SARS-CoV-2 using RNA-Seq experiments. We identified 34 differential ASE (DASE) sites in 13 genes (HLA-A, HLA-B, HLA-C, BRD2, EHD2, GFM2, GSPT1, HAVCR1, MAT2A, NQO2, SUPT6H, TNFRSF11A, UMPS), all of which are enriched in protein binding functions and play a role in COVID-19. Most DASE sites were assigned to the MHC class I locus and were predominantly upregulated upon infection. DASE sites in the MHC class I locus also occur in iPSC-derived airway epithelium basal cells infected with SARS-CoV-2. Using an RNA-Seq haplotype reconstruction approach, we found DASE sites and adjacent eSNVs in phase (i.e., predicted on the same DNA strand), demonstrating differential haplotype expression upon infection. We found a bias towards the expression of the HLA alleles with a higher binding affinity to SARS-CoV-2 epitopes. Independent of gene expression compensation, SARS-CoV-2 infection of human lung cell lines induces transcriptional allelic switching at the MHC loci. This suggests a response mechanism to SARS-CoV-2 infection that swaps HLA alleles with poor epitope binding affinity, an expectation supported by publicly available proteome data.
Deep Coverage and Quantification of the Bone Proteome Provides Enhanced Opportunities for New Discoveries in Skeletal Biology and Disease
Authors: Rose Jacob P. , Schurman Charles A. , King Christina D. , Bons Joanna , Burton Jordan B. , Patel Sandip K. , O’Broin Amy , Alliston Tamara , Schilling Birgit 
Published: November 2022

AbstractDysregulation of cell signaling in chondrocytes and in bone cells, such as osteocytes, osteoblasts, osteoclasts, and an elevated burden of senescent cells in cartilage and bone, are implicated in osteoarthritis (OA). Mass spectrometric analyses provides a crucial molecular tool-kit to understand complex signaling relationships in age-related diseases, such as OA. Here we introduce a novel mass spectrometric workflow to promote proteomic studies of bone and cartilage. This workflow uses highly specialized steps, including extensive overnight demineralization, pulverization, and incubation for 72 h in 6 M guanidine hydrochloride and EDTA, followed by proteolytic digestion. Analysis on a high-resolution Orbitrap Eclipse and Orbitrap Exploris 480 mass spectrometer using Data-Independent Acquisition (DIA) provides deep coverage of the bone proteome, and preserves post-translational modifications, such as hydroxyproline. A spectral library-free quantification strategy, directDIA, identified and quantified over 2,000 protein groups (with ≥ 2 unique peptides) from calcium-rich bone matrices. Key components identified were proteins of the extracellular matrix (ECM), bone-specific proteins (e.g., secreted protein acidic and cysteine rich, SPARC, and bone sialoprotein 2, IBSP), and signaling proteins (e.g., transforming growth factor beta-2, TGFB2), and lysyl oxidase homolog 2 (LOXL2), an important protein in collagen crosslinking. Post-translational modifications (PTMs) were identified without the need for specific enrichment. This includes collagen hydroxyproline modifications, chemical modifications for collagen self-assembly and network formation. Multiple senescence factors were identified, such as complement component 3 (C3) protein of the complement system and many matrix metalloproteinases, that might be monitored during age-related bone disease progression. Our innovative workflow yields in-depth protein coverage and quantification strategies to discover underlying biological mechanisms of bone aging and to provide tools to monitor therapeutic interventions. These novel tools to monitor the bone proteome open novel horizons to investigate bone-specific diseases, many of which are age-related.
Single-cell multi-omics reveals dynamics of purifying selection of pathogenic mitochondrial DNA across human immune cells
Authors: Lareau Caleb A. , Dubois Sonia M. , Buquicchio Frank A. , Hsieh Yu-Hsin , Garg Kopal , Kautz Pauline , Nitsch Lena , Praktiknjo Samantha D. , Maschmeyer Patrick , Verboon Jeffrey M. , Gutierrez Jacob C. , Yin Yajie , Fiskin Evgenij , Luo Wendy , Mimitou Eleni , Muus Christoph , Malhotra Rhea , Parikh Sumit , Fleming Mark D. , Oevermann Lena , Schulte Johannes , Eckert Cornelia , Kundaje Anshul , Smibert Peter , Satpathy Ansuman T. , Regev Aviv , Sankaran Vijay G. , Agarwal Suneet , Ludwig Leif S. 
Published: November 2022

AbstractCells experience intrinsic and extrinsic pressures that affect their proclivity to expand and persistin vivo. In congenital disorders caused by loss-of-function mutations in mitochondrial DNA (mtDNA), metabolic vulnerabilities may result in cell-type specific phenotypes and depletion of pathogenic alleles, contributing to purifying selection. However, the impact of pathogenic mtDNA mutations on the cellular hematopoietic landscape is not well understood. Here, we establish a multi-omics approach to quantify deletions in mtDNA alongside cell state features in single cells derived from Pearson syndrome patients. We resolve the interdependence between pathogenic mtDNA and lineage, including purifying selection against deletions in effector/memory CD8 T-cell populations and recent thymic emigrants and dynamics in other hematopoietic populations. Our mapping of lineage-specific purifying selection dynamics in primary cells from patients carrying pathogenic heteroplasmy provides a new perspective on recurrent clinical phenotypes in mitochondrial disorders, including cancer and infection, with potential broader relevance to age-related immune dysfunction.
Systematic Approach Identifies Multiple Transcription Factor Perturbations That Rejuvenate Replicatively Aged Human Skin Fibroblasts
Authors: Sengstack Janine , Zheng Jiashun , Mobaraki Michael , Lin Jue , Deng Changhui , Li Hao 
Published: November 2022

AbstractRejuvenation, long a quixotic dream, recently became a possibility through exciting new approaches to counteract aging. For example, parabiosis and partial reprogramming through overexpressing four stem cell transcription factors (Yamanaka factors) both rejuvenate organisms and cells1–5. We hypothesize there are many other genetic solutions to human cell rejuvenation, and some solutions may be safer and more potent than current gene targets. We set out to develop a systematic approach to identify novel genes that, when overexpressed or repressed, reprogram the global gene expression of a cell back to a younger state. Using the Hayflick model of human cell replicative aging, we performed a Perturb-seq screen of 200 transcription factors (TFs) selected through a combination of bioinformatic analysis and literature search. We identified dozens of potentially rejuvenating TFs—those that when overexpressed or repressed in late passage cells reprogrammed global gene expression patterns back to an earlier passage state. We further validated four top TF perturbations through molecular phenotyping of various aging hallmarks. Late passage cells either overexpressing EZH2 or E2F3 or repressing STAT3 or ZFX had more cell division, less senescence, improved proteostasis, and enhanced mitochondrial function. These TF perturbations led to similar downstream gene expression programs. In addition, the rejuvenating effects of these TFs were independent of telomeres. We believe our general approach for identifying rejuvenating factors can be applied to other model systems, and some of the top TF perturbations we discovered will lead to future research in novel, safer rejuvenation therapies.