bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells
Authors: Hargrave Kerrie E , Worrell Julie C , Pirillo Chiara , Brennan Euan , Masdefiol Garriga Andreu , Gray Joshua I , Purnell Thomas , Roberts Edward W , MacLeod Megan KL 
Published: September 2023

AbstractInfluenza A virus (IAV) infection leads to the formation of mucosal memory CD4 T cells that can protect the host. An in-depth understanding of the signals that shape memory cell development is required for more effective vaccine design. We have examined the formation of memory CD4 T cells in the lung following IAV infection of mice, characterising changes to the lung landscape and immune cell composition. IAV-specific CD4 T cells were found throughout the lung at both primary and memory time points. These cells were found near lung airways and in close contact with a range of immune cells including macrophages, dendritic cells, and B cells. Interactions between lung IAV-specific CD4 T cells and MHCII+ cells during the primary immune response were important in shaping the subsequent memory pool. Treatment with an anti-MHCII blocking antibody increased the proportion of memory CD4 T cells found at lung airways but reduced interferon-g expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of PD1 than other IAV-specific CD4 T cells and PD1+ memory CD4 T cells were located further away from MHCII+ cells than their PD1-negative counterparts. This distinction in location was lost in mice treated with anti-MHCII antibody. These data suggest that sustained antigen presentation in the lung impacts on the formation of memory CD4 T cells by regulating their cytokine production and location.
Optimal Sampling Rate for 3D Single Molecule Localization
Authors: Chang Huanzhi , Fu Shuang , Li Yiming 
Published: September 2023

AbstractResolution of single molecule localization microscopy (SMLM) depends on the localization accuracy, which can be improved by utilizing engineered point spread functions (PSF) with delicate shapes. However, the intrinsic pixelation effect of the detector sensor will deteriorate PSFs under different sampling rates. The influence of the pixelation effect to the achieved 3D localization accuracy for different PSF shapes under different signal to background ratio (SBR) and pixel dependent readout noise has not been investigated in detail so far. In this work, we proposed a framework to characterize the 3D localization accuracy of pixelated PSF at different sampling rates. Four different PSFs (astigmatic PSF, double helix (DH) PSF, Tetrapod PSF and 4Pi PSF) were evaluated and the pixel size with optimal 3D localization performance were derived. This work provides a theoretical guide for the optimal design of sampling rate for 3D super resolution imaging.
The role of learning in the evolution of status signalling: a modeling approach
Authors: Quiñones Andrés E. , Bshary Redouan , Cadena C. Daniel 
Published: September 2023

AbstractAdaptive behavioural responses often depend on qualities of the interacting partner of an individual. For example, when competing for resources, an individual might be better off escalating fights with individuals of lower quality, while restraining from fighting individuals of higher quality. Communication systems involving signals of quality allow individuals to reduce uncertainty regarding the fighting ability of their partners and make more adaptive behavioral decisions. However, dishonest individuals can destabilize such communications systems. An open question is whether cognitive mechanisms, such as learning, can maintain the honesty of signals, thus favoring their evolutionary stability. We present evolutionary simulations where individuals can produce a signal proportional to their quality and learn along their lifetime the best response to the signals emitted by their peers. Our simulations replicate previous results where the handicap principle mediates the evolution of signals. In our simulations learning on the receiver side can mediate the evolution of signals of quality on the sender side. When the cost of the signal is proportional to the quality of the sender, all individuals in populations are honest signalers. In contrast to traditional models which predict the absence of signals when the cost is not proportional to the quality of the signaler, our model revealed that learning facilitates the evolution of a polymorphism in which populations comprise both honest and dishonest signalers. We argue that learning may have a role in the evolution and dynamics of a wide range of communication systems and more generally in behavioral responses.
Global regulators facilitate adaptation to a phenotypic trade-off
Authors: Deyell Matthew , Opuu Vaitea , Griffiths Andrew D. , Tans Sander J. , Nghe Philippe 
Published: September 2023

AbstractOrganisms depend on their ability to balance multiple phenotypes by evolutionary adaptation. For instance, cellular growth and movement jointly enable critical processes including microbial colonization and cancer invasiveness. Growth and movement are known to be controlled by local regulators that target single operons, as well as by global regulators that impact hundreds of genes. However, how these different levels of regulation interplay during evolution is unclear. Using Escherichia coli growth and motility as a model system, we show that global regulators enable the adaptation of two phenotypes bound by a trade-off, where improvement in one causes deterioration in the other. We measured how CRISPR-mediated knockdowns of global and local transcription factors impact growth and motility in different environments. We find that local regulators mostly modulate motility, while global regulators jointly modulate growth and motility. Genetic perturbations display complex high order interactions between genes and environments. Nevertheless, gene perturbations display consistent patterns in the growth-motility space when grouped by their position in the regulatory hierarchy. These patterns constrain evolutionary scenarios, where local regulators are typically mutated first to optimize motility, then global regulators allow cells to adjust the trade-off between growth and motility. These findings overall highlight the role of pleiotropic regulators for coordinating phenotypic responses in complex environments.
Divide-and-conquer quantum algorithm for hybridde novogenome assembly of short and long reads
Authors: Fang Jing-Kai , Lin Yue-Feng , Huang Jun-Han , Chen Yibo , Fan Gao-Ming , Sun Yuhui , Feng Guanru , Guo Cong , Meng Tiejun , Zhang Yong , Xu Xun , Xiang Jingen , Li Yuxiang 
Published: September 2023

AbstractComputational biology holds immense promise as a domain that can leverage quantum advantages due to its involvement in a wide range of challenging computational tasks. Researchers have recently explored the applications of quantum computing in genome assembly implementation. However, the issue of repetitive sequences remains unresolved. In this paper, we propose a hybrid assembly quantum algorithm using high-accuracy short reads and error-prone long reads to deal with sequencing errors and repetitive sequences. The proposed algorithm builds upon the variational quantum eigensolver and utilizes divide-and-conquer strategies to approximate the ground state of larger Hamiltonian while conserving quantum resources. Using simulations of 10-qubit quantum computers, we address problems as large as 140 qubits, yielding optimal assembly results. The convergence speed is significantly improved via the problem-inspired ansatz based on the known information about the assembly problem. Besides, entanglement within quantum circuits is qualitatively verified to notably accelerate the assembly path optimization.
A unifying model that explains the origins of human inverted copy number variants
Authors: Brewer Bonita J. , Dunham Maitreya J. , Raghuraman M. K. 
Published: September 2023

AbstractWith the release of the telomere-to-telomere human genome sequence and the availability of both long-read sequencing and optical genome mapping techniques, the identification of copy number variants and other structural variants is providing new insights into human genetic disease. Different mechanisms have been proposed to account for the novel junctions in these complex architectures, including aberrant forms of DNA replication, non-allelic homologous recombination and various pathways that repair DNA breaks. Here we have focused on a set of structural variants that include an inverted segment and propose that they share a common initiating event: an inverted triplication with long, unstable palindromic junctions. The secondary rearrangement of these palindromes gives rise to the various forms of inverted structural variants. We postulate that this same mechanism (ODIRA: Origin Dependent Inverted Repeat Amplification) that creates the inverted copy number variants in inherited syndromes also generates the palindromes found in cancers.
Disparities in seizure outcomes revealed by large language models
Authors: Xie Kevin , Ojemann William K.S. , Gallagher Ryan S. , Lucas Alfredo , Hill Chloé E. , Hamilton Roy H. , Johnson Kevin B. , Roth Dan , Litt Brian , Ellis Colin A. 
Published: September 2023

AbstractObjectiveLarge-language models (LLMs) in healthcare have the potential to propagate existing biases or introduce new ones. For people with epilepsy, social determinants of health are associated with disparities in access to care, but their impact on seizure outcomes among those with access to specialty care remains unclear. Here we (1) evaluated our validated, epilepsy-specific LLM for intrinsic bias, and (2) used LLM-extracted seizure outcomes to test the hypothesis that different demographic groups have different seizure outcomes.MethodsFirst, we tested our LLM for intrinsic bias in the form of differential performance in demographic groups by race, ethnicity, sex, income, and health insurance in manually annotated notes. Next, we used LLM-classified seizure freedom at each office visit to test for outcome disparities in the same demographic groups, using univariable and multivariable analyses.ResultsWe analyzed 84,675 clinic visits from 25,612 patients seen at our epilepsy center 2005-2022. We found no differences in the accuracy, or positive or negative class balance of outcome classifications across demographic groups. Multivariable analysis indicated worse seizure outcomes for female patients (OR 1.33, p = 3x10-8), those with public insurance (OR 1.53, p = 2x10-13), and those from lower-income zip codes (OR ≥ 1.22, p ≤ 6.6x10-3). Black patients had worse outcomes than White patients in univariable but not multivariable analysis (OR 1.03, p = 0.66).SignificanceWe found no evidence that our LLM was intrinsically biased against any demographic group. Seizure freedom extracted by LLM revealed disparities in seizure outcomes across several demographic groups. These findings highlight the critical need to reduce disparities in the care of people with epilepsy.Key PointsWe used large language models (LLMs) and natural language processing to extract seizure outcomes from clinical note text.We found no evidence of intrinsic bias in the LLM algorithm, in that it performed similarly across all demographic groups.Using LLM-extracted seizure outcomes, female sex, public insurance, and lower income zip- codes were associated with higher likelihood of seizures at each visit.Black race was associated with higher likelihood of seizures in univariable but not multivariable analysis.These findings highlight the critical need to reduce disparities in the care of people with epilepsy.
Peripheral Blood Single-Cell Sequencing Uncovers Common and Specific Immune Aberrations in Fibrotic Lung Diseases
Authors: Zhao Amy Y. , Unterman Avraham , Abu Hussein Nebal , Sharma Prapti , Flint Jasper , Yan Xiting , Adams Taylor S. , Justet Aurelien , Sumida Tomokazu S. , Zhao Jiayi , Schupp Jonas C. , Raredon Micha Sam B. , Ahangari Farida , Zhang Yingze , Buendia-Roldan Ivette , Adegunsoye Ayodeji , Sperling Anne I. , Prasse Antje , Ryu Changwan , Herzog Erica , Selman Moises , Pardo Annie , Kaminski Naftali 
Published: September 2023

AbstractRationale and ObjectivesThe extent and commonality of peripheral blood immune aberrations in fibrotic interstitial lung diseases are not well characterized. In this study, we aimed to identify common and distinct immune aberrations in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (FHP) using cutting-edge single-cell profiling technologies.MethodsSingle-cell RNA sequencing was performed on patients and healthy controls’ peripheral blood and bronchoalveolar lavage samples using 10X Genomics 5’ gene expression and V(D)J profiling. Cell type composition, transcriptional profiles, cellular trajectories and signaling, and T and B cell receptor repertoires were studied. The standard Seurat R pipeline was followed for cell type composition and differential gene expression analyses. Transcription factor activity was imputed using the DoRothEA-VIPER algorithm. Pseudotime analyses were conducted using Monocle3, while RNA velocity analyses were performed with Velocyto, scVelo, and CellRank. Cell-cell connectomics were assessed using the Connectome R package. V(D)J analyses were conducted using CellRanger and Immcantation frameworks. Across all analyses, disease group differences were assessed using the Wilcoxon rank-sum test.Measurements and Main Results327,990 cells from 83 samples were profiled. Overall, changes in monocytes were common to IPF and FHP, whereas lymphocytes exhibited disease-specific aberrations. Both diseases displayed enrichment of CCL3hi/CCL4hiCD14+ monocytes (p<2.2e-16) and S100AhiCD14+ monocytes (p<2.2e-16) versus controls. Trajectory and RNA velocity analysis suggested that pro-fibrotic macrophages observed in BAL originated from peripheral blood monocytes. Lymphocytes exhibited disease-specific aberrations, with CD8+ GZMKhiT cells and activated B cells primarily enriched in FHP patients. V(D)J analyses revealed unique T and B cell receptor complementarity-determining region 3 (CDR3) amino acid compositions (p<0.05) in FHP and significant IgA enrichment in IPF (p<5.2e-7).ConclusionsWe identified common and disease-specific immune mechanisms in IPF and FHP; S100Ahimonocytes and SPP1himacrophages are common to IPF and FHP, whereas GMZKhiT lymphocytes and T and B cell receptor repertoires were unique in FHP. Our findings open novel strategies for the diagnosis and treatment of IPF and FHP.
Phase-separating fusion proteins drive cancer by dysregulating transcription through ectopic condensates
Authors: Farahi Nazanin , Lazar Tamas , Tompa Peter , Mészáros Bálint , Pancsa Rita 
Published: September 2023

AbstractNumerous cellular processes rely on biomolecular condensates formed through liquid-liquid phase separation (LLPS), thus, perturbations of LLPS underlie various diseases. We found that proteins initiating LLPS are frequently implicated in somatic cancers, even surpassing their involvement in neurodegeneration. Cancer-associated LLPS scaffolds are connected to all cancer hallmarks and tend to be oncogenes with dominant genetic effects lacking therapeutic options. Since most of them act as oncogenic fusion proteins (OFPs), we undertook a systematic analysis of cancer driver OFPs by assessing their module-level molecular functions. We identified both known and novel combinations of molecular functions that are specific to OFPs and thus have a high potential for driving tumorigenesis. Protein regions driving condensate formation show an increased association with DNA- or chromatin-binding domains of transcription regulators within OFPs, indicating a common molecular mechanism underlying several soft tissue sarcomas and hematologic malignancies where phase-separation-prone OFPs form abnormal, ectopic condensates along the DNA, and thereby dysregulate gene expression programs.
Data from Entomological Collections of Aedes (Diptera: Culicidae) in a post-epidemic area of Chikungunya, City of Kinshasa, Democratic Republic of Congo
Authors: Nsabatien Victoire , Zanga Josue , Agossa Fiacre , Mvuama Nono , Bamba Maxwell , Mansiangi Osée , Mbashi Leon , Mvudi Vanessa , Diza Glodie , Kantin Dorcas , Basosila Narcisse , Lukoki Hyacinthe , Bokulu Arsene , Bosulu Christelle , Bukaka Erick , Nagahuedi Jonas , Palata Jean Claude , Metelo Emery 
Published: September 2023

AbstractArbovirus epidemics (e.g. Chikungunya, dengue, West Nile, Yellow Fever, and Zika), are a growing threat in Africa in areas whereAedes(Ae.)aegyptiandA. albopictusare present.The lack of complete sampling of these two vectors limits our ability to understand their propagation dynamics in areas at risk from arboviruses. Here, we describe for the first time the geographical distribution of two arbovirus vectors (Ae. aegyptiandAe. albopictus) in a chikungunya post-epidemic zone in the provincial city of Kinshasa, Democratic Republic of Congo between 2020 and 2022. In total 6,943 observations were reported using larval capture and human capture on landing methods. These data are published in the public domain as a Darwin Core archive in the Global Biodiversity Information Facility. The results of this study potentially provide important information for further basic and advanced studies on the ecology and phenology of these vectors, as well as on vector dynamics after an epidemic period.Subject AreasEcology, Biodiversity, TaxonomyData description
Test-retest reliability of spectral parameterization by 1/fcharacterization usingSpecParam
Authors: McKeown Daniel J. , Finley Anna J. , Kelley Nicholas J. , Cavanagh James F. , Keage Hannah A. D. , Baumann Oliver , Schinazi Victor R. , Moustafa Ahmed A. , Angus Douglas J 
Published: September 2023

ABSTRACTSpecParam(formally known asFOOOF) allows for the refined measurements of electroencephalography periodic and aperiodic activity, and potentially provides a non-invasive measurement of excitation:inhibition balance. However, little is known about the psychometric properties of this technique. This is integral for understanding the usefulness ofSpecParamas a tool to determine differences in measurements of cognitive function, and electroencephalography activity. We used intraclass correlation coefficients (ICC) to examine the test-retest reliability of parameterized activity across three sessions (90 minutes apart and 30 days later) in 49 healthy young adults at rest with eyes open (EO), eyes closed (EC), and during three EC cognitive tasks including subtraction (Math), music recall (Music), and episodic memory (Memory). ICCs were good for the aperiodic exponent and offset (ICCs > .70) and parameterized periodic activity (ICCs > .66 for alpha and beta power, central frequency, and bandwidth) across conditions. Across all three sessions,SpecParamperformed poorly in EO (40% of participants had poor fits over non-central sites) and had poor test-retest reliability for parameterized periodic activity.SpecParammostly provides reliable metrics of individual differences in parameterized neural activity. More work is needed to understand the suitability of EO resting data for parameterization usingSpecParam.
Redox Active Plant Phenolic, Acetosyringone, for Electrogenetic Signaling
Authors: Zakaria Fauziah Rahma , Chen Chen-Yu , Li Jinyang , Wang Sally , Payne Gregory F. , Bentley William E. 
Published: September 2023

AbstractRedox is a unique, programmable modality capable of bridging communication between biology and electronics. Previous studies have shown that theE. coliredox-responsive OxyRS regulon can be re-wired to accept electrochemically generated hydrogen peroxide (H2O2) as an inducer of gene expression. Here we report that the redox-active phenolic plant signaling molecule acetosyringone (AS) can also induce gene expression from the OxyRS regulon. AS must be oxidized, however, as the reduced state present under normal conditions cannot induce gene expression. Thus, AS serves as a “pro-signaling molecule” that can be activated by its oxidation - in our case by application of oxidizing potential to an electrode. We show that the OxyRS regulon is not induced electrochemically if the imposed electrode potential is in the mid-physiological range. Electronically sliding the applied potential to either oxidative or reductive extremes induces this regulon but through different mechanisms: reduction of O2to form H2O2or oxidation of AS. Fundamentally, this work reinforces the emerging concept that redox signaling depends more on molecular activities than molecular structure. From an applications perspective, the creation of an electronically programmed “pro-signal” dramatically expands the toolbox for electronic control of biological responses in microbes, including in complex environments, cell-based materials, and biomanufacturing.
Flexible 3-D Electrochemical Impedance Spectroscopy Sensors Incorporating Phase Delay for Comprehensive Characterization of Atherosclerosis
Authors: Chen Michael , Neverova Natalia , Xu Shili , Suwannaphoom Krit , Lluri Gentian , Tamboline Mikayla , Duarte Sandra , Fishbein Michael C. , Luo Yuan , Packard René R. Sevag 
Published: September 2023

ABSTRACTBackgroundDistinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies.We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology.MethodsMale New Zealand White rabbits (n=16) were placed on a high-fat diet for 4 or 8 weeks, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwentin vivomicro-PET imaging of the abdominal aorta with68Ga-DOTATATE,18F-NaF, and18F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histological analyses. Analyses were performed blindly.ResultsPhase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r=0.883 at 1 kHz,P=0.004) and %stenosis (r=0.901 at 0.25 kHz,P=0.002), similar to IVUS. Moreover, impedance was associated with markers of plaque activity including macrophage infiltration (r=0.813 at 10 kHz,P=0.008) and macrophage/smooth muscle cell (SMC) ratio (r=0.813 at 25 kHz,P=0.026).68Ga-DOTATATE correlated with intimal macrophage infiltration (r=0.861,P=0.003) and macrophage/SMC ratio (r=0.831,P=0.021),18F-NaF with SMC infiltration (r=-0.842,P=0.018), and18F-FDG correlated with macrophage/SMC ratio (r=0.787,P=0.036).ConclusionsEIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS as a comprehensive modality for evaluation of human coronary artery disease.GRAPHICAL ABSTRACTHIGHLIGHTSElectrochemical impedance spectroscopy (EIS) characterizes both anatomic features – via phase delay; and inflammatory activity – via impedance profiles, of underlying atherosclerosis.EIS can serve as an integrated, comprehensive metric for atherosclerosis evaluation by capturing morphological and compositional plaque characteristics that otherwise require multiple imaging modalities to obtain.Translation of these findings from animal models to human coronary artery disease may provide an additional strategy to help guide clinical management.