bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-GlcNAcylation of Sox2 at threonine 258 regulates the self-renewal and early cell fate of embryonic stem cells
Authors: Kim Dong Keon , Lee Jang-Seok , Lee Eun Young , Jang Hansol , Han Suji , Kim Hee Yeon , Hwang In-Young , Choi Ji-Woong , Shin Hyun Mu , You Hye Jin , Youn Hong-Duk , Jang Hyonchol 
Published: November 2021

AbstractSox2 is a core transcription factor in embryonic stem cells (ESCs), and O-GlcNAcylation is a type of post-translational modification of nuclear-cytoplasmic proteins. Although both factors play important roles in the maintenance and differentiation of ESCs and the serine 248 (S248) and threonine 258 (T258) residues of Sox2 are modified by O-GlcNAcylation, the function of Sox2 O-GlcNAcylation is unclear. Here, we show that O-GlcNAcylation of Sox2 at T258 regulates mouse ESC self-renewal and early cell fate. ESCs in which wild-type Sox2 was replaced with the Sox2 T258A mutant exhibited reduced self-renewal, whereas ESCs with the Sox2 S248A point mutation did not. ESCs with the Sox2 T258A mutation heterologously introduced using the CRISPR/Cas9 system, designated E14-Sox2TA/WT, also exhibited reduced self-renewal. RNA sequencing analysis under self-renewal conditions showed that upregulated expression of early differentiation genes, rather than a downregulated expression of self-renewal genes, was responsible for the reduced self-renewal of E14-Sox2TA/WT cells. There was a significant decrease in ectodermal tissue and a marked increase in cartilage tissue in E14-Sox2TA/WT-derived teratomas compared with normal E14 ESC-derived teratomas. RNA sequencing of teratomas revealed that genes related to brain development had generally downregulated expression in the E14-Sox2TA/WT-derived teratomas. Our findings using the Sox2 T258A mutant suggest that Sox2 T258 O-GlcNAc has a positive effect on ESC self-renewal and plays an important role in the proper development of ectodermal lineage cells. Overall, our study directly links O-GlcNAcylation and early cell fate decisions.
Interactions between gastric microbiota and metabolites in gastric cancer
Authors: Dai Daofeng , Yang Yan , Yu Jieqing , Dang Tianfeng , Qin Wenjing , Teng Lisong , Ye Jing , Jiang Hongqun 
Published: November 2021

AbstractThe development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.
Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models
Authors: Hakim Chady H. , Kumar Sandeep R. P. , Pérez-López Dennis O. , Wasala Nalinda B. , Zhang Dong , Yue Yongping , Teixeira James , Pan Xiufang , Zhang Keqing , Million Emily D. , Nelson Christopher E. , Metzger Samantha , Han Jin , Louderman Jacqueline A. , Schmidt Florian , Feng Feng , Grimm Dirk , Smith Bruce F. , Yao Gang , Yang N. Nora , Gersbach Charles A. , Chen Shi-jie , Herzog Roland W. , Duan Dongsheng 
Published: November 2021

AbstractAdeno-associated virus (AAV)-mediated CRISPR-Cas9 editing holds promise to treat many diseases. The immune response to bacterial-derived Cas9 has been speculated as a hurdle for AAV-CRISPR therapy. However, immunological consequences of AAV-mediated Cas9 expression have thus far not been thoroughly investigated in large mammals. We evaluate Cas9-specific immune responses in canine models of Duchenne muscular dystrophy (DMD) following intramuscular and intravenous AAV-CRISPR therapy. Treatment results initially in robust dystrophin restoration in affected dogs but also induces muscle inflammation, and Cas9-specific humoral and cytotoxic T-lymphocyte (CTL) responses that are not prevented by the muscle-specific promoter and transient prednisolone immune suppression. In normal dogs, AAV-mediated Cas9 expression induces similar, though milder, immune responses. In contrast, other therapeutic (micro-dystrophin and SERCA2a) and reporter (alkaline phosphatase, AP) vectors result in persistent expression without inducing muscle inflammation. Our results suggest Cas9 immunity may represent a critical barrier for AAV-CRISPR therapy in large mammals.
Mechanisms for destabilisation of RNA viruses at air-water and liquid-liquid interfaces
Authors: Brackley C. A. , Lips A. , Morozov A. , Poon W. C. K. , Marenduzzo D. 
Published: November 2021

AbstractUnderstanding the interactions between viruses and surfaces or interfaces is important, as they provide the principles underpinning the cleaning and disinfection of contaminated surfaces. Yet, the physics of such interactions is currently poorly understood. For instance, there are longstanding experimental observations suggesting that the presence of air-water interfaces can generically inactivate and kill viruses, yet the mechanism underlying this phenomenon remains unknown. Here we use theory and simulations to show that electrostatics may provide one such mechanism, and that this is very general. Thus, we predict that the electrostatic free energy of an RNA virus should increase by several thousands of kBT as the virion breaches an air-water interface. We also show that the fate of a virus approaching a generic liquid-liquid interface depends strongly on the detailed balance between interfacial and electrostatic forces, which can be tuned, for instance, by choosing different media to contact a virus-laden respiratory droplet. Tunability arises because both the electrostatic and interfacial forces scale similarly with viral size. We propose that these results can be used to design effective strategies for surface disinfection.
ATR inhibition enables complete tumour regression in ALK-driven NB mouse models
Authors: Szydzik Joanna , Lind Dan E. , Arefin Badrul , Kurhe Yeshwant , Umapathy Ganesh , Siaw Joachim Tetteh , Claeys Arne , Gabre Jonatan L. , Van den Eynden Jimmy , Hallberg Bengt , Palmer Ruth H. 
Published: November 2021

AbstractHigh-risk neuroblastoma (NB) often involvesMYCNamplification as well as mutations inALK. Currently, high-risk NB presents significant clinical challenges, and additional therapeutic options are needed. Oncogenes likeMYCNandALKresult in increased replication stress in cancer cells, offering therapeutically exploitable options. We have pursued phosphoproteomic analyses highlighting ATR activity in ALK-driven NB cells, identifying the BAY1895344 ATR inhibitor as a potent inhibitor of NB cell growth and proliferation. Using RNA-Seq, proteomics and phosphoproteomics we characterize NB cell and tumour responses to ATR inhibition, identifying key components of the DNA damage response as ATR targets in NB cells. ATR inhibition also produces robust responses in mouse models. Remarkably, a 2-week combined ATR/ALK inhibition protocol leads to complete tumor regression in two independent genetically modified mouse NB models. These results suggest that NB patients, particularly in high-risk groups with oncogene-induced replication stress, may benefit from ATR inhibition as therapeutic intervention.
Solution-processable and functionalizable ultra-high molecular weight polymers via topochemical synthesis
Authors: Anderson Christopher L. , Li He , Jones Christopher G. , Teat Simon J. , Settineri Nicholas S. , Dailing Eric A. , Liang Jiatao , Mao Haiyan , Yang Chongqing , Klivansky Liana M. , Li Xinle , Reimer Jeffrey A. , Nelson Hosea M. , Liu Yi 
Published: November 2021

AbstractTopochemical polymerization reactions hold the promise of producing ultra-high molecular weight crystalline polymers. However, the totality of topochemical polymerization reactions has failed to produce ultra-high molecular weight polymers that are both soluble and display variable functionality, which are restrained by the crystal-packing and reactivity requirements on their respective monomers in the solid state. Herein, we demonstrate the topochemical polymerization reaction of a family of para-azaquinodimethane compounds that undergo facile visible light and thermally initiated polymerization in the solid state, allowing for the first determination of a topochemical polymer crystal structure resolved via the cryoelectron microscopy technique of microcrystal electron diffraction. The topochemical polymerization reaction also displays excellent functional group tolerance, accommodating both solubilizing side chains and reactive groups that allow for post-polymerization functionalization. The thus-produced soluble ultra-high molecular weight polymers display superior capacitive energy storage properties. This study overcomes several synthetic and characterization challenges amongst topochemical polymerization reactions, representing a critical step toward their broader application.
Synergistic insights into human health from aptamer- and antibody-based proteomic profiling
Authors: Pietzner Maik , Wheeler Eleanor , Carrasco-Zanini Julia , Kerrison Nicola D. , Oerton Erin , Koprulu Mine , Luan Jian’an , Hingorani Aroon D. , Williams Steve A. , Wareham Nicholas J. , Langenberg Claudia 
Published: November 2021

AbstractAffinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques—the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays—to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein–phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer’s disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.
Evaluation of endogenous miRNA reference genes across different zebrafish strains, developmental stages and kidney disease models
Authors: Siegerist Florian , Lange Tim , Iervolino Anna , Koppe Thor Magnus , Zhou Weibin , Capasso Giovambattista , Endlich Karlhans , Endlich Nicole 
Published: November 2021

AbstractThe majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseases in vivo. Unfortunately, there is no consensus about a proper normalization strategy of RT-qPCR-based miRNA expression data in zebrafish. In this study we analyzed 9 preselected candidates dre-miR-92a-3p, dre-miR-206-3p, dre-miR-99-1, dre-miR-92b-3p, dre-miR-363-3p, dre-let-7e, dre-miR-454a, dre-miR-30c-5p, dre-miR-126a-5p for their capability as endogenous reference genes in zebrafish experiments. Expression levels of potential candidates were measured in 3 different zebrafish strains, different developmental stages, and in different kidney disease models by RT-qPCR. Expression values were analyzed with NormFinder, BestKeeper, GeNorm, and DeltaCt and were tested for inter-group differences. All candidates show an abundant expression throughout all samples and relatively high stability. The most stable candidate without significant inter-group differences was dre-miR-92b-3p making it a suitable endogenous reference gene for RT-qPCR-based miR expression zebrafish studies.
Segmentation of infected region in CT images of COVID-19 patients based on QC-HC U-net
Authors: Zhang Qin , Ren Xiaoqiang , Wei Benzheng 
Published: November 2021

AbstractSince the outbreak of COVID-19 in 2019, the rapid spread of the epidemic has brought huge challenges to medical institutions. If the pathological region in the COVID-19 CT image can be automatically segmented, it will help doctors quickly determine the patient’s infection, thereby speeding up the diagnosis process. To be able to automatically segment the infected area, we proposed a new network structure and named QC-HC U-Net. First, we combine residual connection and dense connection to form a new connection method and apply it to the encoder and the decoder. Second, we choose to add Hypercolumns in the decoder section. Compared with the benchmark 3D U-Net, the improved network can effectively avoid vanishing gradient while extracting more features. To improve the situation of insufficient data, resampling and data enhancement methods are selected in this paper to expand the datasets. We used 63 cases of MSD lung tumor data for training and testing, continuously verified to ensure the training effect of this model, and then selected 20 cases of public COVID-19 data for training and testing. Experimental results showed that in the segmentation of COVID-19, the specificity and sensitivity were 85.3% and 83.6%, respectively, and in the segmentation of MSD lung tumors, the specificity and sensitivity were 81.45% and 80.93%, respectively, without any fitting.
Implementation and analysis of quantum computing application to Higgs boson reconstruction at the large Hadron Collider
Authors: Alexiades Armenakas Anthony , Baker Oliver K. 
Published: November 2021

AbstractWith the advent of the High-Luminosity Large Hadron Collider (HL-LHC) era, high energy physics (HEP) event selection will require new approaches to rapidly and accurately analyze vast databases. The current study addresses the enormity of HEP databases in an unprecedented manner—a quantum search using Grover’s Algorithm (GA) on an unsorted database, ATLAS Open Data, from the ATLAS detector. A novel method to identify rare events at 13 TeV in CERN’s LHC using quantum computing (QC) is presented. As indicated by the Higgs boson decay channel $$H\rightarrow ZZ^*\rightarrow 4l$$

H
→
Z

Z
∗

→
4
l

, the detection of four leptons in one event may be used to reconstruct the Higgs boson and, more importantly, evince Higgs boson decay to some new phenomena, such as $$H\rightarrow ZZ_d \rightarrow 4l$$

H
→
Z

Z
d

→
4
l

. Searching the dataset for collisions resulting in detection of four leptons using a Jupyter Notebook, a classical simulation of GA, and several quantum computers with multiple qubits, the current application was found to make the proper selection in the unsorted dataset. Quantum search efficacy was analyzed for the incoming HL-LHC by implementing the QC method on multiple classical simulators and IBM’s quantum computers with the IBM Qiskit Open Source Software. The current QC application provides a novel, high-efficiency alternative to classical database searches, demonstrating its potential utility as a rapid and increasingly accurate search method in HEP.
Comparative transcriptome analysis of fiber and nonfiber tissues to identify the genes preferentially expressed in fiber development in Gossypium hirsutum
Authors: Yang Jiangtao , Gao Lihua , Liu Xiaojing , Zhang Xiaochun , Wang Xujing , Wang Zhixing 
Published: November 2021

AbstractCotton is an important natural fiber crop and economic crop worldwide. The quality of cotton fiber directly determines the quality of cotton textiles. Identifying cotton fiber development-related genes and exploring their biological functions will not only help to better understand the elongation and development mechanisms of cotton fibers but also provide a theoretical basis for the cultivation of new cotton varieties with excellent fiber quality. In this study, RNA sequencing technology was used to construct transcriptome databases for different nonfiber tissues (root, leaf, anther and stigma) and fiber developmental stages (7 days post-anthesis (DPA), 14 DPA, and 26 DPA) of upland cotton Coker 312. The sizes of the seven transcriptome databases constructed ranged from 4.43 to 5.20 Gb, corresponding to approximately twice the genome size of Gossypium hirsutum (2.5 Gb). Among the obtained clean reads, 83.32% to 88.22% could be compared to the upland cotton TM-1 reference genome. By analyzing the differential gene expression profiles of the transcriptome libraries of fiber and nonfiber tissues, we obtained 1205, 1135 and 937 genes with significantly upregulated expression at 7 DPA, 14 DPA and 26 DPA, respectively, and 124, 179 and 213 genes with significantly downregulated expression. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analyses were performed, which revealed that these genes were mainly involved in catalytic activity, carbohydrate metabolism, the cell membrane and organelles, signal transduction and other functions and metabolic pathways. Through gene annotation analysis, many transcription factors and genes related to fiber development were screened. Thirty-six genes were randomly selected from the significantly upregulated genes in fiber, and expression profile analysis was performed using qRT-PCR. The results were highly consistent with the gene expression profile analyzed by RNA-seq, and all of the genes were specifically or predominantly expressed in fiber. Therefore, our RNA sequencing-based comparative transcriptome analysis will lay a foundation for future research to provide new genetic resources for the genetic engineering of improved cotton fiber quality and for cultivating new transgenic cotton germplasms for fiber quality improvement.
Reorganization of functional and directed corticomuscular connectivity during precision grip from childhood to adulthood
Authors: Beck Mikkel Malling , Spedden Meaghan Elizabeth , Lundbye-Jensen Jesper 
Published: November 2021

AbstractHow does the neural control of fine movements develop from childhood to adulthood? Here, we investigated developmental differences in functional corticomuscular connectivity using coherence analyses in 111 individuals from four different age groups covering the age range 8–30 y. EEG and EMG were recorded while participants performed a uni-manual force-tracing task requiring fine control of force in a precision grip with both the dominant and non-dominant hand. Using beamforming methods, we located and reconstructed source activity from EEG data displaying peak coherence with the EMG activity of an intrinsic hand muscle during the task. Coherent cortical sources were found anterior and posterior to the central sulcus in the contralateral hemisphere. Undirected and directed corticomuscular coherence was quantified and compared between age groups. Our results revealed that coherence was greater in adults (20–30 yo) than in children (8–10 yo) and that this difference was driven by greater magnitudes of descending (cortex-to-muscle), rather than ascending (muscle-to-cortex), coherence. We speculate that the age-related differences reflect maturation of corticomuscular networks leading to increased functional connectivity with age. We interpret the greater magnitude of descending oscillatory coupling as reflecting a greater degree of feedforward control in adults compared to children. The findings provide a detailed characterization of differences in functional sensorimotor connectivity for individuals at different stages of typical ontogenetic development that may be related to the maturational refinement of dexterous motor control.
A study of awareness on HIV/AIDS among adolescents: A Longitudinal Study on UDAYA data
Authors: Srivastava Shobhit , Chauhan Shekhar , Patel Ratna , Kumar Pradeep 
Published: November 2021

AbstractAcquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus (HIV) poses a severe challenge to healthcare and is a significant public health issue worldwide. This study intends to examine the change in the awareness level of HIV among adolescents. Furthermore, this study examined the factors associated with the change in awareness level on HIV-related information among adolescents over the period. Data used for this study were drawn from Understanding the lives of adolescents and young adults, a longitudinal survey on adolescents aged 10–19 in Bihar and Uttar Pradesh. The present study utilized a sample of 4421 and 7587 unmarried adolescent boys and girls, respectively aged 10–19 years in wave-1 and wave-2. Descriptive analysis and t-test and proportion test were done to observe changes in certain selected variables from wave-1 (2015–2016) to wave-2 (2018–2019). Moreover, random effect regression analysis was used to estimate the association of change in HIV awareness among unmarried adolescents with household and individual factors. The percentage of adolescent boys who had awareness regarding HIV increased from 38.6% in wave-1 to 59.9% in wave-2. Among adolescent girls, the percentage increased from 30.2 to 39.1% between wave-1 & wave-2. With the increase in age and years of schooling, the HIV awareness increased among adolescent boys ([Coef: 0.05; p < 0.01] and [Coef: 0.04; p < 0.01]) and girls ([Coef: 0.03; p < 0.01] and [Coef: 0.04; p < 0.01]), respectively. The adolescent boys [Coef: 0.06; p < 0.05] and girls [Coef: 0.03; p < 0.05] who had any mass media exposure were more likely to have an awareness of HIV. Adolescent boys' paid work status was inversely associated with HIV awareness [Coef: − 0.01; p < 0.10]. Use of internet among adolescent boys [Coef: 0.18; p < 0.01] and girls [Coef: 0.14; p < 0.01] was positively associated with HIV awareness with reference to their counterparts. There is a need to intensify efforts in ensuring that information regarding HIV should reach vulnerable sub-groups, as outlined in this study. It is important to mobilize the available resources to target the less educated and poor adolescents, focusing on rural adolescents.