bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein MRI Contrast Agents as an Effective Approach for Precision Molecular Imaging
Authors: Li Dongjun , Kirberger Michael , Qiao Jingjuan , Gui Zongxiang , Xue Shenghui , Pu Fan , Jiang Jie , Xu Yiting , Tan Shanshan , Salarian Mani , Ibhagui Oluwatosin , Hekmatyar Khan , Yang Jenny J. 
Published: January 2024

AbstractCancer and other acute and chronic diseases are results of perturbations of common molecular determinants in key biological and signaling processes. Imaging is critical for characterizing dynamic changes in tumors and metastases, the tumor microenvironment, tumor-stroma interactions, and drug targets, at multiscale levels. Magnetic resonance imaging (MRI) has emerged to be a primary imaging modality for both clinical and preclinical applications due to its advantages over other modalities, including sensitivity to soft tissues, nondepth limitations, and the use of nonionizing radiation. However, extending the application of MRI to achieve both qualitative and quantitative precise molecular imaging with the capability to quantify molecular biomarkers for early detection, staging, and monitoring therapeutic treatment requires the capacity to overcome several major challenges including the trade-off between metal-binding affinity and relaxivity, which is an issue frequently associated with small chelator contrast agents. In this review, we will introduce the criteria of ideal contrast agents for precision molecular imaging and discuss the relaxivity of current contrast agents with defined first shell coordination water molecules. We will then report our advances in creating a new class of protein-targeted MRI contrast agents (ProCAs) with contributions to relaxivity largely derived from the secondary sphere and correlation time. We will summarize our rationale, design strategy, and approaches to the development and optimization of our pioneering ProCAs with desired high relaxivity, metal stability, and molecular biomarker-targeting capability, for precision MRI. From first generation (ProCA1) to third generation (ProCA32), we have achieved dual high r1and r2values that are 6- to 10-fold higher than clinically approved contrast agents at magnetic fields of 1.5 T, and their relaxivity values at high field are also significantly higher, which enables high resolution during small animal imaging. Further engineering of multiple targeting moieties enables ProCA32 agents that have strong biomarker-binding affinity and specificity for an array of key molecular biomarkers associated with various chronic diseases, while maintaining relaxation and exceptional metal-binding and selectivity, serum stability, and resistance to transmetallation, which are critical in mitigating risks associated with metal toxicity. Our leading product ProCA32.collagen has enabled the first early detection of liver metastasis from multiple cancers at early stages by mapping the tumor environment and early stage of fibrosis from liver and lung in vivo, with strong translational potential to extend to precision MRI for preclinical and clinical applications for precision diagnosis and treatment.
Physiological 68Ga-PSMA-11 Uptake in Dural Venous Sinuses
Authors: Kulkarni Mukta , Joshi Prathamesh Vijay , Kumar Kritik 
Published: January 2024

Abstract
We describe hitherto unreported physiological low-grade 68Ga-PSMA-11 uptake in dural sinuses of patients who underwent 68Ga-PSMA-11 PET/CT for evaluation of prostate carcinoma. A strong positive correlation was found between SUVmax of tracer uptake in dural sinuses and SUVmax of blood pool activity in superior vena cava. Low-grade 68Ga-PSMA-11 uptake seen in dural sinuses is physiological and is most likely result of venous blood pool activity. Such uptake should not be interpreted as pathological. Knowledge of such physiological uptake is essential for optimal interpretation of PSMA PET/CT images and differentiating physiological versus pathological uptake.
Rare Findings of Gallbladder Metastasis From Cutaneous Melanoma on 18F-FDG PET/CT Imaging
Authors: Zhou Jing , Zhao Yigang 
Published: January 2024

Abstract
We present the imaging findings of a 77-year-old man with a history of malignant cutis melanoma that metastasized to the gallbladder. A restaging 18F-FDG PET/CT scan showed uneven thickening and elevated 18F-FDG uptake in the gallbladder wall. Subsequently, the patient underwent laparoscopic cholecystectomy, and histopathologic findings confirmed the diagnosis of metastatic melanoma of the gallbladder.
Technical Considerations in EEG Source Imaging
Authors: Brinkmann Benjamin H. 
Published: January 2024

Summary:
EEG source imaging is an established technique for identifying the origin of interictal and ictal epileptiform discharges in patients with epilepsy, and it is an important tool in neurophysiology research. Accurate and reliable EEG source imaging requires appropriate choices of how the head, skull, and scalp are modeled, and understanding of the different approaches to modeling is important to guide these choices. Similarly, numerous different approaches to modeling the electrical sources within the brain exist, and appropriate understanding of the strengths and limitations of each are essential to obtaining accurate, reliable, and interpretable solutions. This review aims to describe the essential theoretical basis for these head and source models while also discussing the practical implications of each in clinical or research applications.
DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases
Authors: Zeng Yang C. , Young Olivia J. , Si Longlong , Ku Min Wen , Isinelli Giorgia , Rajwar Anjali , Jiang Amanda , Wintersinger Chris M. , Graveline Amanda R. , Vernet Andyna , Sanchez Melinda , Ryu Ju Hee , Kwon Ick Chan , Goyal Girija , Ingber Donald E. , Shih William M. 
Published: January 2024

AbstractCurrent SARS-CoV-2 vaccines have demonstrated robust induction of neutralizing antibodies and CD4+T cell activation, however CD8+responses are variable, and the duration of immunity and protection against variants are limited. Here we repurposed our DNA origami vaccine platform, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific HR2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+T cells, and CD8+T cells in naïve mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular immune responses in human cells. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities. The programmability of this platform underscores its potential utility in addressing future pandemics.
Histone acetyltransferase HAF2 associates with PDC to control H3K14ac and H3K23ac in ethylene response
Authors: Chen Chia-Yang , Shao Zhengyao , Wang Guihua , Zhao Bo , Hardtke Haley A. , Leong Josh , Zhou Tiffany , Zhang Y.Jessie , Qiao Hong 
Published: January 2024

AbstractEthylene plays its essential roles in plant development, growth, and defense responses by controlling the transcriptional reprogramming, in which EIN2-C-directed regulation of histone acetylation is the first key-step for chromatin to perceive ethylene signaling. However, the histone acetyltransferase in this process remains unknown. Here, we identified histone acetyltransferase HAF2, and mutations in HAF2 confer plants with ethylene insensitivity. Furthermore, we found that HAF2 interacts with EIN2-C in response to ethylene. Biochemical assays demonstrated that the bromodomain of HAF2 binds to H3K14ac and H3K23ac peptides with a distinct affinity for H3K14ac; the HAT domain possesses acetyltransferase catalytic activity for H3K14 and H3K23 acetylation, with a preference for H3K14. ChIP-seq results provide additional evidence supporting the role of HAF2 in regulating H3K14ac and H3K23ac levels in response to ethylene. Finally, our findings revealed that HAF2 co-functions with pyruvate dehydrogenase complex (PDC) to regulate H3K14ac and H3K23ac in response to ethylene in an EIN2 dependent manner. Overall, this research reveals that HAF2 as a histone acetyltransferase that forms a complex with EIN2-C and PDC, collectively governing histone acetylation of H3H14ac and H3K23ac, preferentially for H3K14 in response to ethylene.
Variation of C-terminal domain governs RNA polymerase II genomic locations and alternative splicing in eukaryotic transcription
Authors: Zhang Qian , Kim Wantae , Panina Svetlana , Mayfield Joshua E. , Portz Bede , Zhang Y. Jessie 
Published: January 2024

AbstractThe C-terminal domain of RPB1 (CTD) orchestrates transcription by recruiting regulators to RNA Pol II upon phosphorylation. Recent insights highlight the pivotal role of CTD in driving condensate formation on gene loci. Yet, the molecular mechanism behind how CTD-mediated recruitment of transcriptional regulators influences condensates formation remains unclear. Our study unveils that phosphorylation reversibly dissolves phase separation induced by the unphosphorylated CTD. Phosphorylated CTD, upon specific association with transcription regulatory proteins, forms distinct condensates from unphosphorylated CTD. Function studies demonstrate CTD variants with diverse condensation properties in vitro exhibit difference in promoter binding and mRNA co-processing in cells. Notably, varying CTD lengths lead to alternative splicing outcomes impacting cellular growth, linking the evolution of CTD variation/length with the complexity of splicing from yeast to human. These findings provide compelling evidence for a model wherein post-translational modification enables the transition of functionally specialized condensates, highlighting a co-evolution link between CTD condensation and splicing.
BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population
Authors: Iqbal Najeeha Talat , Ahmed Kumail , Sattar Tehniat , Aziz Fatima , Hussain Rabia 
Published: January 2024

AbstractBackgroundDuring the current COVID-19 pandemic, the rate of morbidity and mortality was considerably lower in BCG vaccinated countries like Pakistan. BCG has been shown to provide cross protection to both disseminated TB as well as non related viral infections in BCG vaccinated children which is consistent with COVID-19 morbidity in the younger age group. Recently, this cross protection was attributed to trained immunity (TI) associated with BCG recall responses in the innate arm of the immune system. Little is known about the longevity of BCG Trained Immunity (TI) beyond early childhood.ObjectiveTo assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections.Study DesignIn this cross-sectional study, healthy young adults and adolescents (n=20) were recruited from 16–40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition.MethodsBCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network {macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)} and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay.ResultsSignificant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold for IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG.ConclusionThe presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro-and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.
Comprehensive and accurate genome analysis at scale using DRAGEN accelerated algorithms
Authors: Behera Sairam , Catreux Severine , Rossi Massimiliano , Truong Sean , Huang Zhuoyi , Ruehle Michael , Visvanath Arun , Parnaby Gavin , Roddey Cooper , Onuchic Vitor , Cameron Daniel L , English Adam , Mehtalia Shyamal , Han James , Mehio Rami , Sedlazeck Fritz J 
Published: January 2024

AbstractResearch and medical genomics require comprehensive and scalable solutions to drive the discovery of novel disease targets, evolutionary drivers, and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size (e.g., SNV/SV) or location (e.g., repeats). Here we present DRAGEN that utilizes novel methods based on multigenomes, hardware acceleration, and machine learning based variant detection to provide novel insights into individual genomes with ∼30min computation time (from raw reads to variant detection). DRAGEN outperforms all other state-of-the-art methods in speed and accuracy across all variant types (SNV, indel, STR, SV, CNV) and further incorporates specialized methods to obtain key insights in medically relevant genes (e.g., HLA, SMN, GBA). We showcase DRAGEN across 3,202 genomes and demonstrate its scalability, accuracy, and innovations to further advance the integration of comprehensive genomics for research and medical applications.
A revised single-cell transcriptomic atlas ofXenopusembryo reveals new differentiation dynamics
Authors: Petrova Kseniya , Tretiakov Maksym , Kotov Aleksandr , Monsoro-Burq Anne H. , Peshkin Leonid 
Published: January 2024

AbstractThis paper introduces an updated single-cell atlas for pivotal developmental stages inXenopus, encompassing gastrulation, neurulation, and early tailbud. Notably surpassing its predecessor, the new atlas enhances gene mapping, read counts, and gene/cell type nomenclature. Leveraging the latest Xenopus tropicalis genome version, alongside advanced alignment pipelines and machine learning for cell type assignment, this release maintains consistency with previous cell type annotations while rectifying nomenclature issues. Employing an unbiased approach for cell type assignment proves especially apt for embryonic contexts, given the considerable number of non-terminally differentiated cell types. An alternative cell type attribution here adopts a fuzzy, non-deterministic stance, capturing the transient nature of early embryo progenitor cells by presenting an ensemble of types in superposition. The value of the new resource is emphasized through numerous examples, with a focus on previously unexplored germ cell populations where we uncover novel transcription onset features. Offering interactive exploration via a user-friendly web portal and facilitating complete data downloads, this atlas serves as a comprehensive and accessible reference.
Viral proteins activate PARIS-mediated tRNA degradation and viral tRNAs rescue infection
Authors: Burman Nathaniel , Belukhina Svetlana , Depardieu Florence , Wilkinson Royce A. , Skutel Mikhail , Santiago-Frangos Andrew , Graham Ava B. , Livenskyi Alexei , Chechenina Anna , Morozova Natalia , Zahl Trevor , Henriques William S. , Buyukyoruk Murat , Rouillon Christophe , Shyrokova Lena , Kurata Tatsuaki , Hauryliuk Vasili , Severinov Konstantin , Groseille Justine , Thierry Agnès , Koszul Romain , Tesson Florian , Bernheim Aude , Bikard David , Wiedenheft Blake , Isaev Artem 
Published: January 2024

AbstractViruses compete with each other for limited cellular resources, and some viruses deliver defense mechanisms that protect the host from competing genetic parasites. PARIS is a defense system, often encoded in viral genomes, that is composed of a 53 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB). Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving the host tRNALys. Phage T5 subverts PARIS immunity through expression of a tRNALysvariant that prevents PARIS-mediated cleavage, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids.
STING Licensing of Type I Dendritic Cells Potentiates Antitumor Immunity
Authors: Wang Jian , Li Suxin , Wang Maggie , Wang Xu , Chen Shuqing , Sun Zhichen , Ren Xiubao , Huang Gang , Sumer Baran D. , Yan Nan , Fu Yang-Xin , Gao Jinming 
Published: January 2024

AbstractStimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP (cGAMP) in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations including cancer cells with distinct cellular functions such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether and which subsets of immune cells, stromal cells, or cancer cells are particularly important for STING-mediated antitumor immunity. Here using a polymeric STING-activating nanoparticle (PolySTING) with a “shock-and-lock” dual activation mechanism, we show type 1 conventional dendritic cell (cDC1) is essential for STING-mediated rejection of multiple established and metastatic murine tumors. STING status in the host but not in the cancer cells (Tmem173-/-) is important for antitumor efficacy. Specific depletion of cDC1 (Batf3-/-) or STING deficiency in cDC1 (XCR1creSTINGfl/fl) abolished PolySTING efficacy, whereas depletion of other myeloid cells had little effect. Adoptive transfer of wildtype cDC1 inBatf3-/-mice restored antitumor efficacy while transfer of cDC1 with STING or IRF3 deficiency failed to rescue. PolySTING induced a specific chemokine signature in wildtype but notBatf3-/-mice. Multiplexed immunohistochemistry analysis of STING-activating cDC1s in resected tumors correlates with patient survival while also showing increased expressions after neoadjuvant pembrolizumab therapy in non-small cell lung cancer patients. Therefore, we have defined that a subset of myeloid cells is essential for STING-mediated antitumor immunity with associated biomarkers for prognosis.One Sentence SummaryA “shock-and-lock” nanoparticle agonist induces direct STING signaling in type 1 conventional dendritic cells to drive antitumor immunity with defined biomarkers
MapTurns: mapping the structure, H-bonding and contexts of beta turns in proteins
Authors: Newell Nicholas E. 
Published: January 2024

AbstractMotivationBeta turns are the most common type of secondary structure in proteins after alpha helices and beta sheets and play many key structural and functional roles. Turn backbone (BB) geometry has been classified at multiple levels of precision, but the current picture of side chain (SC) structure and interaction in turns is incomplete, because the distribution of SC conformations associated with each sequence motif has commonly been represented only by a static image of a single, typical structure for each turn BB geometry, and only motifs which specify single amino acids have been systematically investigated. Furthermore, no general evaluation has been made of the SC interactions between turns and the structures in their BB neighborhoods. Finally, the visualization and comparison of the wide range of turn conformations has been hampered by the almost exclusive characterization of turn structure in BB dihedral-angle (Ramachandran) space.ResultsThis work introduces MapTurns, a web server for motif maps, which employ a turn-local Euclidean-space coordinate system and a global turn alignment to comprehensively map the distributions of BB and SC structure and H-bonding associated with sequence motifs in beta turns and their local BB contexts. Maps characterize many new SC motifs, provide detailed rationalizations of sequence preferences, and support mutational analysis and the general study of SC interactions, and they should prove useful in applications such as protein design.Availability and ImplementationMapTurns is available atwww.betaturn.comalong with a broad, map-based survey of SC motifs in beta turns. HTML/Javascript code for a sample map is available at:https://github.com/nenewell/MapTurns/tree/main.Supplementary InformationSupplementary File 1: Methods.
Capturing Snapshots of Nucleosomal H2A K13/K15 Ubiquitination Mediated by the Monomeric E3 Ligase RNF168
Authors: Ai Huasong , Tong Zebin , Deng Zhiheng , Shi Qiang , Tao Shixian , Liang Jiawei , Sun Maoshen , Wu Xiangwei , Zheng Qingyun , Liang Lujun , Li Jia-Bin , Gao Shuai , Tian Changlin , Liu Lei , Pan Man 
Published: January 2024

AbstractsThe DNA damage repair regulatory protein RNF168, a monomeric RING-type E3 ligase, plays a crucial role in regulating cell fate and DNA repair by specific and efficient ubiquitination of the adjacent Lys13 and Lys15 sites at the H2A N-terminal tail. However, understanding how RNF168 coordinates with its cognate E2 enzyme UbcH5c to ubiquitinate H2AK13/15 site-specifically has long been hampered by the lack of high-resolution structures of RNF168 and UbcH5c∼Ub in complex with nucleosomes. Here, we developed mechanism-based chemical trapping strategies and determined the cryo-EM structures of the RNF168/UbcH5c–Ub/NCP complex captured in transient H2AK13/15 monoubiquitination and adjacent dual-monoubiquitination reactions. Our structural analysis revealed that RNF168 stably binds to the nucleosomal H2A–H2B acidic patch through a basic helix with multiple interactions, which positions the UbcH5c active centre directly over the H2A N-terminus, providing a “helix-anchoring” mode for monomeric E3 ligase RNF168 on nucleosome in contrast to the “compass-binding” mode of dimeric E3 ligases. Furthermore, our chemically synthesized ubiquitinated histones have enabled the elucidation of the efficiency of Ub installation and the interplay between the initial and subsequent Ub modifications on the adjacent H2A K13 and K15 sites. Overall, our work not only provides structural snapshots of H2A K13/K15 site-specific monoubiquitination and adjacent dual-monoubiquitination, but also offers a near-atomic resolution structural framework for understanding how pathogenic mutations or physiological modifications affect the molecular function of RNF168 in H2A K13/15 ubiquitination.