bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel antibody language model accelerates IgG screening and design for broad-spectrum antiviral therapy
Authors: Almubarak Hannah Faisal , Tan Wuwei , Hoffmann Andrew D. , Sun Yuanfei , Wei Juncheng , El-Shennawy Lamiaa , Squires Joshua R. , Dashzeveg Nurmaa K. , Simonton Brooke , Jia Yuzhi , Iyer Radhika , Xu Yanan , Nicolaescu Vlad , Elli Derek , Randall Glenn C. , Schipma Matthew J. , Swaminathan Suchitra , Ison Michael G. , Liu Huiping , Fang Deyu , Shen Yang 
Published: March 2024

AbstractTherapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline AbGen that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. Our AbGen centers around a novel antibody language model (AbLM) that is pretrained on 12 million generic protein domain sequences and fine-tuned on 4,000+ paired VH-VL sequences, with IgG-specific CDR-masking and VH-VL cross-attention. AbLM provides a latent space of IgG sequence embeddings for AbGen, including (a) landscapes of IgGs’ activities in neutralizing the wild-type virus are analyzed through structure prediction for IgG and IgG-antigen (viral protein spike’s receptor binding domain, RBD) interactions; and (b) landscapes of IgGs’ susceptibility in neutralizing variant viruses are predicted through Gaussian process regression, despite that as few as 14 clinical antibodies’ responses to variants of concern are available. The AbGen pipeline was applied to over 1300 IgG sequences we collected from RBD-binding B cells of convalescent patients. With experimental validations, AbGen efficiently prioritized IgG candidates against a broad spectrum of viral variants (wildtype, Delta, and Omicron), preventing the infection of host cellsin vitroand hACE2 transgenic micein vivo. Compared to other existing protein language models that require 10-100 times more model parameters, AbLM improved the precision from around 50% to 75% to predict IgGs with low variant susceptibility. Furthermore, AbGen enables structure-based computational protein redesign for selected IgG clones with single amino acid substitutions at the RBD-binding interface that doubled the IgG blockade efficacy for one of the severe, therapy-resistant strains - Delta (B.1.617). Our work expedites applications of artificial intelligence in antibody screen and re- design combining data-driven protein language models and Kriging for antibody sequence analysis and activity prediction, in synergy with physics-driven protein docking and design for antibody-antigen interface analyses and functional optimization.
The complement regulator CD55 modulates TLR9 signaling and supports survival in marginal zone B cells
Authors: Lee Iris , Ling Ivana , Verma Sonam , Blanche Wumei , Pham Christine T.N. , Kendall Peggy L. 
Published: March 2024

AbstractMarginal zone (MZ) B cells bridge innate and adaptive immunity by sensing bloodborne antigens and producing rapid antibody and cytokine responses. CD55 is a membrane-bound complement regulator that interferes with complement activation, an important component of innate immunity. CD55 also regulates adaptive immunity—CD55 downregulation is critical for germinal center reactions. MZ B cells also express low CD55, but its role in MZ B cell function is unknown. Using germline knockout mice, we found that similar numbers of MZ B cells are initially established in 3-week-old CD55-deficient mice compared to wild-type (WT) mice. However, MZ B cells fail to accumulate as mice age and undergo increased apoptosis. Followingex vivostimulation of MZ B cells through Toll-like receptor 9, we observed a proinflammatory phenotype with increased IL-6 expression. These findings demonstrate a critical role for CD55 in supporting MZ B cell survival while also regulating cellular function.
Repeated Exposure Decreases Aesthetic Chills Likelihood but Increases Intensity
Authors: Schoeller F. , Christov-Moore L. , Lynch C. , Jain A. , Diot T. , Reggente N. 
Published: March 2024

AbstractAesthetic chills are a peak emotional response to affectively charged stimuli such as music, films, or speech. This study investigates the impact of repeated exposure on the frequency and intensity of aesthetic chills. Through a longitudinal approach, we quantified changes in chill likelihood, intensity, and pleasure across multiple exposures, focusing on audio stimuli. Participants (n = 58) were randomly exposed to 6 chill-evoking stimuli pre-validated on the population of interest, in a counterbalanced order. Our findings revealed a significant decrease in the likelihood of experiencing chills with repeated exposure, suggesting habituation to chills itself or potential fatigue in response to aesthetic stimuli. The study also identified distinct demographic and psychophysiological response patterns across different participant groups, indicating variability in chill responses. These results provide insights into the dynamic nature of aesthetic experiences and their underlying neural mechanisms, with implications for understanding emotional and reward processing in psychophysiology.
A trait-based taxonomic data base for the order Schizomida (Arachnida) with descriptions of a new fossil species from Kachin amber and the female ofSurazomus palenqueVillarreal, Miranda & Giupponi 2016
Authors: Müller Sandro P , Magnussen Ilian De Francesco , Gearty William , Dupérré Nadine , Hammel Jörg U , Kotthoff Ulrich 
Published: March 2024

AbstractDespite a global distribution throughout the tropics and sub-tropics, the order Schizomida (Arachnida) is heavily understudied and the phylogeny of the group is poorly understood. Identification keys are only available for some regions or genera but not for the entire order. (1) comprehensively reviewed the entire schizomid fauna and established a suite of characters to define all genera known at this time. This suite of characters still depicts the foundation of modern descriptions, supplemented by recently established characters, most of them documenting setation patterns on pedipalps, flagellum and chelicerae. In this paper, we present the Schizomida Trait Data Base (STDB) containing data for 25 characters based on the entire body of schizomid literature. Characters were chosen based on their use for modern taxonomic description and availability of the data. The STDB is a powerful tool that can be used by both amateurs and experienced researchers to categorise newly found specimens, both extant and fossil, down to genus level easily. Analysis using the new database gives insight into biogeographical patterns of characters. Furthermore, we are describing a new species,†Annazomus jamesi,a fossil specimen from Burmese (Kachin) amber and investigate a small collection of extant schizomids from Ecuador, which includes the previously unrecorded female ofSurazomus palenque,herein described for the first time. The taxonomic assignment of both specimens is based on the STDB, highlighting the utility of the new data base approach to schizomid systematics.Arachnids, biogeography, Cretaceous, data base, fossil, new species, palaeontology, Schizomida, statistics, taxonomy
Localized estimation of event-related neural source activity from simultaneous MEG-EEG with a recurrent neural network
Authors: O’Reilly Jamie A. , Zhu Judy D. , Sowman Paul F. 
Published: March 2024

AbstractEstimating intracranial current sources underlying the electromagnetic signals observed from extracranial sensors is a perennial challenge in non-invasive neuroimaging. Established solutions to this inverse problem treat time samples independently without considering the temporal dynamics of event-related brain processes. This paper describes current source estimation from simultaneously recorded magneto- and electro-encephalography (MEEG) using a recurrent neural network (RNN) that learns sequential relationships from neural data. The RNN was trained in two phases: (1) pre-training and (2) transfer learning with L1 regularization applied to the source estimation layer. Performance of using scaled labels derived from MEEG, magnetoencephalography (MEG), or electroencephalography (EEG) were compared, as were results from volumetric source space with free dipole orientation and surface source space with fixed dipole orientation. Exact low-resolution electromagnetic tomography (eLORETA) and mixed-norm L1/L2 (MxNE) source estimation methods were also applied to these data for comparison with the RNN method. The RNN approach outperformed other methods in terms of output signal-to-noise ratio, correlation and mean-squared error metrics evaluated against ground-truth event-related field (ERF) and event-related potential (ERP) waveforms. Using MEEG labels with fixed-orientation surface sources produced the most consistent estimates. To estimate sources of ERF and ERP waveforms, the RNN generates temporal dynamics within its internal computational units, driven by sequential structure in neural data used as training labels. It thus provides a data-driven model of computational transformations from psychophysiological events into corresponding event-related neural signals, which is unique among MEG and EEG source reconstruction solutions.
High-fidelity annotated genome of the polyploid and quarantine root-knot nematode,Meloidogyne enterolobii
Authors: Poullet Marine , Gopal Hemanth , Rancurel Corinne , Sallaberry Marine , Lopez-Roques Celine , Lledo Joanna , Kiewnick Sebastian , Danchin Etienne GJ 
Published: March 2024

AbstractRoot-knot nematodes of the genusMeloidogyneare obligatory plant endoparasites that cause substantial economic losses to the agricultural production and impact the global food supply. These plant parasitic nematodes belong to the most widespread and devastating genus worldwide, yet few measures of control are available. The most efficient way to control root-knot nematodes (RKN) is deployment of resistance genes in plants. However, current resistance genes that control otherMeloidogynespecies are mostly inefficient onM. enterolobii. Consequently,M. enterolobiiwas listed as a European Union quarantine pest implementing regulation. To gain insight into the molecular characteristics underlying its parasitic success, exploring the genome ofM. enterolobiiis essential. Here, we report a high-quality genome assembly ofMeloidogyne enterolobiiusing the high-fidelity long-read sequencing technology developed by Pacific Biosciences, combined with a gap-aware sequence transformer, DeepConsensus. The resulting genome assembly spans 273 Mbp with 556 contigs, a GC% of 30 ± 0.042 and an N50 value of 2.11Mb, constituting a useful platform for comparative, population and functional genomics.
Time-dependent enhancement of mRNA vaccines by 4-1BB costimulation
Authors: Sanchez Sarah , Dangi Tanushree , Awakoaiye Bakare , Irani Nahid , Fourati Slim , Richner Justin , Penaloza-MacMaster Pablo 
Published: March 2024

AbstractmRNA vaccines have demonstrated efficacy against COVID-19. However, concerns regarding waning immunity and breakthrough infections have motivated the development of next-generation vaccines with enhanced efficacy. In this study, we investigated the impact of 4-1BB costimulation on immune responses elicited by mRNA vaccines in mice. We first vaccinated mice with an mRNA vaccine encoding the SARS-CoV-2 spike antigen like the Moderna and Pfizer-BioNTech vaccines, followed by administration of 4-1BB costimulatory antibodies at various times post-vaccination. Administering 4-1BB costimulatory antibodies during the priming phase did not enhance immune responses. However, administering 4-1BB costimulatory antibodies after 96 hours elicited a significant improvement in CD8 T cell responses, leading to enhanced protection against breakthrough infections. A similar improvement in immune responses was observed with multiple mRNA vaccines, including vaccines against common cold coronavirus, human immunodeficiency virus (HIV), and arenavirus. These findings demonstrate a time-dependent effect by 4-1BB costimulation and provide insights for developing improved mRNA vaccines.
Inflammation promotes aging-associated oncogenesis in the lung
Authors: Pham-Danis Catherine , Chia Shi B , Scarborough Hannah A , Danis Etienne , Nemkov Travis , Kleczko Emily K , Navarro Andre , Goodspeed Andrew , Bonney Elizabeth A. , Dinarello Charles A. , Marchetti Carlo , Nemenoff Raphael A. , Hansen Kirk , DeGregori James 
Published: March 2024

ABSTRACTBackgroundLung cancer is the leading cause of cancer death in the world. While cigarette smoking is the major preventable factor for cancers in general and lung cancer in particular, old age is also a major risk factor. Aging-related chronic, low-level inflammation, termed inflammaging, has been widely documented; however, it remains unclear how inflammaging contributes to increased lung cancer incidence.AimTo establish connections between aging-associated changes in the lungs and cancer risk.MethodsWe analyzed public databases of gene expression for normal and cancerous human lungs and used mouse models to understand which changes were dependent on inflammation, as well as to assess the impact on oncogenesis.ResultsAnalyses of GTEx and TCGA databases comparing gene expression profiles from normal lungs, lung adenocarcinoma, lung squamous cell carcinoma of subjects across age groups revealed upregulated pathways such as inflammatory response, TNFA signaling via NFκB, and interferon-gamma response. Similar pathways were identified comparing the gene expression profiles of young and old mouse lungs. Transgenic expression of alpha 1 antitrypsin (AAT) partially reverses increases in markers of aging-associated inflammation and immune deregulation. Using an orthotopic model of lung cancer using cells derived from EML4-ALK fusion-induced adenomas, we demonstrated an increased tumor outgrowth in lungs of old mice while NLRP3 knockout in old mice decreased tumor volumes, suggesting that inflammation contributes to increased lung cancer development in aging organisms.ConclusionsThese studies reveal how expression of an anti-inflammatory mediator (AAT) can reduce some but not all aging-associated changes in mRNA and protein expression in the lungs. We further show that aging is associated with increased tumor outgrowth in the lungs, which may relate to an increased inflammatory microenvironment.
Chromosome-level genome assembly of the disco clam,Ctenoides ales, a first for the bivalve order Limida
Authors: McElroy Kyle E , Masonbrink Rick , Chudalayandi Sivanandan , Severin Andrew J , Serb Jeanne M 
Published: March 2024

ABSTRACTThe bivalve subclass Pteriomorphia, which includes the economically important scallops, oysters, mussels, and ark clams, exhibits extreme ecological, morphological, and behavioral diversity. Among this diversity are five morphologically distinct eye types, making Pteriomorphia an excellent setting to explore the molecular basis for the evolution of novel traits. Of pteriomorphian bivalves, Limida is the only order lacking genomic resources, greatly limiting the potential phylogenomic analyses related to eyes and phototransduction. Here, we present the first limid genome assembly, the disco clam,Ctenoides ales, which is characterized by invaginated eyes, exceptionally long tentacles, and a flashing light display. This genome assembly was constructed with PacBio long reads and Dovetail Omni-CTMproximity-ligation sequencing. The final assembly is ∼2.3Gb and over 99% of the total length is contained in 18 pseudomolecule scaffolds. We annotated 41,064 protein coding genes and report a BUSCO completeness of 91.9% for metazoa_obd10. Additionally, we report a completely annotated mitochondrial genome, also a first for Limida. The ∼20Kb mitogenome has 12 protein coding genes, 22 tRNAs, 2 rRNA genes, and a 1,589 bp duplicated sequence containing the origin of replication. TheC. alesnuclear genome size is substantially larger than other pteriomorphian genomes, mainly accounted for by transposable element sequences. We inventoried the genome for opsins, the signaling proteins that initiate phototransduction, and found that, unlike its closest eyed-relatives, the scallops,C. aleslacks duplication of the rhabdomeric Gq-protein coupled opsin that is typically used for invertebrate vision. In fact,C. aleshas uncharacteristically few opsins relative to the other pteriomorphian families, all of which have unique expansions of xenopsins, a recently discovered opsin subfamily. This chromosome-level assembly, along with the mitogenome, will be valuable resources for comparative genomics and phylogenetics in bivalves and particularly for the understudied but charismatic limids.SignificanceThis high-quality chromosome-level genome assembly forCtenoides ales, the disco clam, is the first genome sequenced from the bivalve order Limida, the only group of Pteriomorphia – a highly diverse and ecologically important clade – lacking genomic resources. The sequence and annotation of theC. alesgenome will be a useful resource for molluscan phylogenetics and comparative genomics.
CRIPTO promotes extracellular vesicle uptake and activation of cancer associated fibroblasts
Authors: Freeman David W. , Gates Brooke L. , Spendlove Mauri D. , Gulbahce H. Evin , Spike Benjamin T. 
Published: March 2024

ABSTRACTExpression of CRIPTO, a factor involved in embryonic stem cells, fetal development, and wound healing, is tied to poor prognosis in multiple cancers. Prior studies in triple negative breast cancer (TNBC) models showed CRIPTO blockade inhibits tumor growth and dissemination. Here, we uncover a previously unidentified role for CRIPTO in orchestrating tumor-derived extracellular vesicle (TEV) uptake and fibroblast activation through discrete mechanisms. We found a novel mechanism by which CRIPTO drives aggressive TNBC phenotypes, involving CRIPTO-laden TEVs that program stromal fibroblasts, toward cancer associated fibroblast cell states, which in turn prompt tumor cell invasion. CRIPTO-bearing TEVs exhibited markedly elevated uptake in target fibroblasts and activated SMAD2/3 through NODAL-independent and - dependent mechanisms, respectively. Engineered expression of CRIPTO on EVs enhanced the delivery of bioactive molecules.In vivo, CRIPTO levels dictated TEV uptake in mouse lungs, a site of EV-regulated premetastatic niches important for breast cancer dissemination. These discoveries reveal a novel role for CRIPTO in coordinating heterotypic cellular crosstalk which offers novel insights into breast cancer progression, delivery of therapeutic molecules, and new, potentially targetable mechanisms of heterotypic cellular communication between tumor cells and the TME.
The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination
Authors: Nguyen Doan C. , Hentenaar Ian T. , Morrison-Porter Andrea , Solano David , Haddad Natalie S. , Castrillon Carlos , Lamothe Pedro A. , Andrews Joel , Roberts Danielle , Lonial Sagar , Sanz Ignacio , Lee F. Eun-Hyung 
Published: March 2024

AbstractThe goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma cells can be found in the BM. To better understand this paradox, we enrolled 19 healthy adults at 1.5-33 months after SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus-, or SARS-CoV-2-specific antibody secreting cells (ASC) in LLPC (CD19−) and non-LLPC (CD19+) subsets within the BM. All individuals had IgG ASC specific for influenza, tetanus, and SARS-CoV-2 in at least one BM ASC compartment. However, only influenza- and tetanus-specific ASC were readily detected in the LLPC whereas SARS-CoV-2 specificities were mostly excluded. The ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.61, 0.44, and 29.07, respectively. Even in five patients with known PCR-proven history of infection and vaccination, SARS-CoV-2-specific ASC were mostly excluded from the LLPC. These specificities were further validated by using multiplex bead binding assays of secreted antibodies in the supernatants of cultured ASC. Similarly, the IgG ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.66, 0.44, and 23.26, respectively. In all, our studies demonstrate that rapid waning of serum antibodies is accounted for by the inability of mRNA vaccines to induce BM LLPC.
Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms
Authors: Suzuki-Okutani Mie , Okamura Shinya , Tanggis  , Sasaki Hitomi , Lee Suni , Yoshida Akiho , Goto Simon , Matsumoto Mai , Yamawaki Mayuko , Miyazaki Toshiaki , Nakagawa Tatsuya , Ikawa Masahito , Kamitani Wataru , Takekawa Shiro , Yamanishi Koichi , Ebina Hirotaka 
Published: March 2024

AbstractmRNA vaccines against SARS-CoV-2 were rapidly developed and effective during the pandemic. However, some limitations remain to be resolved, such as the short-lived induced immune response and certain adverse effects. Therefore, there is an urgent need to develop new vaccines that address these issues. While live-attenuated vaccines are a highly effective modality, they pose a risk of adverse effects, including virulence reversion. In the current study, we constructed a live-attenuated vaccine candidate, BK2102, combining naturally occurring virulence-attenuating mutations in theNSP14,NSP1, spike andORF7-8coding regions. Intranasal inoculation with BK2102 induced humoral and cellular immune responses in Syrian hamsters without apparent tissue damage in the lungs, leading to protection against a SARS-CoV-2 D614G and an Omicron BA.5 strains. The neutralizing antibodies induced by BK2102 persisted for up to 364 days, which indicated that they confer long-term protection against infection. Furthermore, we confirmed the safety of BK2102 using transgenic (Tg) mice expressing human ACE2 (hACE2), that are highly susceptible to SARS-CoV-2. BK2102 did not kill the Tg mice, even when virus was administered at a dose of 106plaque-forming units (PFU), while 102PFU of the D614G strain or an attenuated strain lacking the furin cleavage site (FCS) of the spike was sufficient to kill mice. These results suggest that BK2102 is a promising live-vaccine candidate strain that confers long-term protection without significant virulence.