bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jupytope: Computational extraction of structural properties of viral epitopes
Authors: Rashid Shamima , Ann Ng Teng , Keong Kwoh Chee 
Published: March 2022

AbstractEpitope residues located on viral surface proteins are of immense interest in immunology and related applications such as vaccine development, disease diagnosis and drug design. Most tools rely on sequence based statistical comparisons, such as information entropy of residue positions in aligned columns to infer location and properties of epitope sites. To facilitate cross-structural comparisons of epitopes on viral surface proteins, a python-based extraction tool implemented with Jupyter notebook is presented (Jupytope). Given a viral antigen structure of interest, a list of known epitope sites and a reference structure, the corresponding epitope structural properties can quickly be obtained. The tool integrates biopython modules for commonly used software such as NACCESS, DSSP as well as residue depth and outputs a list of structure derived properties such as dihedral angles, solvent accessibility, residue depth and secondary structure that can be saved in several convenient data formats. To ensure correct spatial alignment, Jupytope takes a list of given epitope sites and their corresponding reference structure and aligns them before extracting the desired properties. Examples are demonstrated for epitopes of Influenza and SARS-CoV2 viral strains. The extracted properties assist detection of two Influenza subtypes and show potential in distinguishing between four major clades of SARS-CoV2, as compared with randomized labels. The tool will facilitate analytical and predictive works on viral epitopes through the extracted structural information.Key MessagesJupytope combines existing 3D-structural software to extract the properties of viral epitopes into a convenient text or csv file formatThe structural properties serve as parameters or features that quantitatively capture viral epitopesAssociation of structural properties to viral subtypes (for Influenza) or clades (SARS-CoV2) is demonstrated with a simple XGBoost modelStructure datasets mapped to SARS-CoV2 WHO clades and Pango lineages, as well as chain annotations are available for download
Persistent acetylation of histone H3 lysine 56 compromises the activity of DNA replication origins
Authors: Tremblay Roch , Mehrjoo Yosra , Simoneau Antoine , McQuaid Mary E. , Nislow Corey , Giaever Guri , Wurtele Hugo 
Published: March 2022

ABSTRACTInSaccharomyces cerevisiae, newly synthesized histone H3 are acetylated on lysine 56 (H3 K56ac) by the Rtt109 acetyltransferase prior to their deposition on nascent DNA behind replication forks. Two deacetylases of the sirtuin family, Hst3 and Hst4, remove H3 K56ac from chromatin following S phase.hst3Δhst4Δ cells present constitutive H3 K56ac, which sensitizes cells to replicative stress via mechanisms that remain unclear. We performed a screen to identify genes that influence cell fitness upon nicotinamide (NAM)-induced inhibition of sirtuins. The screen revealed thatDBF4heterozygosity causes NAM sensitivity.DBF4andCDC7encode subunits of the Dbf4-dependent kinase, which activates origins of DNA replication. We show that i) cells harboring thedbf4-1orcdc7-4hypomorphic alleles are sensitive to NAM, ii) Rif1, an inhibitor of Cdc7-dependent activation of origins, causes DNA damage and replication defects in NAM-treated cells andhst3Δhst4Δ mutants, and iii)cdc7-4 hst3Δhst4Δ cells display synthetic temperature sensitivity associated with delayed initiation of DNA replication. Such replication defects are not due to activation of the intra-S phase checkpoint but require Rtt109-dependent H3 K56ac. Overall, these results suggest that persistent H3 K56ac sensitizes cells to replicative stress in part by negatively influencing replication origin activity.
Intranasal Nanoemulsion Adjuvanted S-2P Vaccine Demonstrates Protection in Hamsters and Induces Systemic, Cell-Mediated and Mucosal Immunity in Mice
Authors: Ganesan Shyamala , Acosta Hugo , Brigolin Chris , Orange Kallista , Trabbic Kevin , Chen Charles , Lien Chia-En , Lin Yi-Jiun , Lin Meei-Yun , Chuang Ya-Shan , Fattom Ali , Bitko Vira 
Published: March 2022

AbstractWith the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need.
Modeling the effect of cooperativity in ternary complex formation and targeted protein degradation mediated by heterobifunctional degraders
Authors: Park Daniel , Izaguirre Jesus , Coffey Rory , Xu Huafeng 
Published: March 2022

AbstractChemically induced proximity between certain endogenous enzymes and a protein of interest (POI) inside cells may cause post-translational modifications to the POI with biological consequences and potential therapeutic effects. Heterobifunctional (HBF) molecules that bind with one functional part to a target POI and with the other to an E3 ligase induce the formation of a target-HBF-E3 ternary complex, which can lead to ubiquitination and proteasomal degradation of the POI. Targeted protein degra-dation (TPD) by HBFs offers a promising approach to modulating disease-associated proteins, especially those that are intractable using other therapeutic approaches, such as enzymatic inhibition. The three-way interactions among the HBF, the target POI, and the ligase—including the protein-protein interaction (PPI) between the POI and the ligase—contribute to the stability of the ternary complex, manifested as positive or negative binding cooperativity in its formation. How such cooperativity affects HBF-mediated degradation is an open question. In this work, we develop a pharmaco-dynamic model that describes the kinetics of the key reactions in the TPD process, and we use this model to investigate the role of cooperativity in the ternary complex formation and in the target POI degradation. Our model predicts that, under certain conditions, increasing cooperativity may diminish degradation, implying an optimal range of cooperativity values for efficient degradation. We also develop a statistical inference model for determining cooperativity in intracellular ternary complex formation from cellular assay data, and demonstrate it by quantifying the change in cooperativity due to site-directed mutagenesis at the POI-ligase interface of the SMARCA2-ACBI1-VHL ternary complex. Our pharmacodynamic model provides a quantitative framework to dissect the complex HBF-mediated TPD process and may inform the rational design of effective HBF degraders.
Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
Authors: Fang Zhenhao , Peng Lei , Lin Qianqian , Zhou Liqun , Yang Luojia , Feng Yanzhi , Ren Ping , Renauer Paul A. , Park Jonathan J. , Zhou Xiaoyu , Wilen Craig B. , Chen Sidi 
Published: March 2022

AbstractThe Omicron sub-lineage BA.2 of SARS-CoV-2 has recently become dominant across many areas in the world in the on-going waves of COVID-19. Compared to the ancestral/wild-type (WT) virus, Omicron lineage variants, both BA.1 and BA.2, contain high number of mutations, especially in the spike protein, causing significant immune escape that leads to substantial reduction of vaccine and antibody efficacy. Because of this antigenic drift, BA.2 exhibited differential resistance profile to monoclonal antibodies than BA.1. Thus, it is important to understand whether the immunity elicited by currently available vaccines are effective against the BA.2 subvariant. We directly tested the heterotypic vaccination responses against Omicron BA.2, using vaccinated serum from animals receiving WT- and variant-specific mRNA vaccine in lipid nanoparticle (LNP) formulations. Omicron BA.1 and BA.2 antigen showed similar reactivity to serum antibodies elicited by two doses of WT, B.1.351 and B.1.617 LNP-mRNAs. Neutralizing antibody titers of B.1.351 and B.1.617 LNP-mRNA were ~2-fold higher than that of WT LNP-mRNA. Both homologous boosting with WT LNP-mRNA and heterologous boosting with BA.1 LNP-mRNA substantially increased waning immunity of WT vaccinated mice against both BA.1 and BA.2 subvariants. The BA.1 LNP-mRNA booster was ~3-fold more efficient than WT LNP-mRNA at elevating neutralizing antibody titers of BA.2. Together, these data provided a direct preclinical evaluation of WT and variant-specific LNP-mRNAs in standard two-dose and as boosters against BA.1 and BA.2 subvariants.
Increased Circulating miR-155 identifies a subtype of preeclamptic patients
Authors: Wang Zhiyin , Duan Honglei , Wang Yuan , Liu Dan , Cao Chenrui , Dai Yimin , Zhao Guangfeng , Gu Ning , Zhou Yan , Zheng Mingming , Hu Yali 
Published: March 2022

AbstractPreeclampsia is a heterogeneous disorder which affect maternal and fetal outcomes. The current classifications of preeclampsia such as “early-“ and “late-” types, and “mild” and “severe” forms, are too imprecise to delineate the pathophysiology of preeclampsia. Here we reported that roughly one third of preeclampsia patients had high expression of maternal serum miR-155 in the case-control study and longitudinal study. The maternal serum miR-155 increased as early as 11-13+6 weeks of gestation. The patients with high serum miR-155 had severer clinical symptoms such as higher blood pressure and urine protein, and more adverse maternal and fetal outcomes. Moreover, these patients could be clustered as one group according to clinical manifestation by t-distributed stochastic neighbor embedding analysis. Therefore, these data suggest that preeclamptic patients with high maternal serum miR-155 could be viewed as a subtype of preeclampsia.
Global Spatial Transcriptome of Macaque Brain at Single-Cell Resolution
Authors: Chen Ao , Sun Yidi , Lei Ying , Li Chao , Liao Sha , Liang Zhifeng , Lin Feng , Yuan Nini , Li Mei , Wang Kexin , Yang Meisong , Zhang Shuzhen , Zhuang Zhenkun , Meng Juan , Song Qiong , Zhang Yong , Xu Yuanfang , Cui Luman , Han Lei , Yang Hao , Sun Xing , Fei Tianyi , Chen Bichao , Li Wenjiao , Huangfu Baoqian , Ma Kailong , Li Zhao , Lin Yikun , Liu Zhen , Wang He , Zhong Yanqing , Zhang Huifang , Yu Qian , Wang Yaqian , Zhu Zhiyong , Liu Xing , Peng Jian , Liu Chuanyu , Chen Wei , An Yingjie , Xia Shihui , Lu Yanbing , Wang Mingli , Song Xinxiang , Liu Shuai , Wang Zhifeng , Gong Chun , Huang Xin , Yuan Yue , Zhao Yun , Luo Zhenhui , Tan Xing , Liu Jianfeng , Zheng Mingyuan , Li Shengkang , Huang Yaling , Hong Yan , Huang Zirui , Li Min , Zhang Ruiyi , Jin Mengmeng , Li Yan , Zhang Hui , Sun Suhong , Bai Yinqi , Cheng Mengnan , Hu Guohai , Liu Shiping , Wang Bo , Xiang Bin , Li Shuting , Li Huanhuan , Chen Mengni , Wang Shiwen , Zhang Qi , Liu Weibin , Liu Xin , Zhao Qian , Lisby Michael , Wang Jing , Fang Jiao , Lu Zhiyue , Lin Yun , Xie Qing , He Jie , Xu Huatai , Huang Wei , Wei Wu , Yang Huanming , Sun Yangang , Poo Muming , Wang Jian , Li Yuxiang , Shen Zhiming , Liu Longqi , Liu Zhiyong , Xu Xun , Li Chengyu 
Published: March 2022

AbstractGlobal profile of gene expression at single-cell resolution remains to be determined for primates. Using a recently developed technology (“Stereo-seq”), we have obtained a comprehensive single-cell spatial transcriptome map at the whole-brain level for cynomolgus monkeys, with ∼600 genes per cell for 10 μm-thick coronal sections (up to 15 cm2 in size). Large-scale single-nucleus RNA-seq analysis for ∼1 million cells helped to identify cell types corresponding to Stereo-seq gene expression profiles, providing a 3-D cell type atlas of the monkey brain. Quantitative analysis of Stereo-seq data revealed molecular fingerprints that mark distinct neocortical layers and subregions, as well as domains within subcortical structures including hippocampus, thalamus, striatum, cerebellum, hypothalamus and claustrum. Striking whole-brain topography and coordinated patterns were found in the expression of genes encoding receptors and transporters for neurotransmitters and neuromodulators. These results pave the way for cellular and molecular understanding of organizing principles of the primate brain.
From neural border to migratory stage: A comprehensive single cell roadmap of the timing and regulatory logic driving cranial and vagal neural crest emergence
Authors: Kotov Aleksandr , Alkobtawi Mansour , Seal Subham , Kappès Vincent , Ruiz Sofia Medina , Arbès Hugo , Harland Richard , Peshkin Leonid , Monsoro-Burq Anne H. 
Published: March 2022

AbstractNeural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning and large-scale experimental validation to provide a comprehensive GRN underlying neural crest fate diversification from induction to early migration stages in the frog Xenopus tropicalis. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple and converging gene programs. Transcription factor connectome and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent lineage persisting until after epithelial-mesenchymal transition. We decipher the circuits driving cranial and vagal neural crest formation and provide a broadly applicable strategy for investigating SC transcriptomes in vertebrate GRNs in development, evolution, and disease.
Identifying targetable metabolic dependencies across colorectal cancer progression
Authors: Legge Danny N. , Stanko Ewelina , Holt Amy K. , Bull Caroline J. , Collard Tracey J. , Kollareddy Madhu , Bellamy Jake , Groves Sarah , Ma Eric H. , Hazelwood Emma , Qualtrough David , Amulic Borko , Malik Karim , Williams Ann C. , Jones Nicholas , Vincent Emma E. 
Published: March 2022

AbstractColorectal cancer (CRC) is a multi-stage process initiated through the formation of a benign adenoma, progressing to an invasive carcinoma and finally metastatic spread. Tumour cells must adapt their metabolism to support the energetic and biosynthetic demands associated with disease progression. As such, targeting cancer cell metabolism is a promising therapeutic avenue in CRC. However, to identify tractable nodes of metabolic vulnerability specific to CRC stage, we must understand how metabolism changes during CRC development. Here, we use a unique model system – comprising human early adenoma to late adenocarcinoma. We show that adenoma cells transition to elevated glycolysis at the early stages of tumour progression but maintain oxidative metabolism. Progressed adenocarcinoma cells rely more on glutamine-derived carbon to fuel the TCA cycle, whereas glycolysis and TCA cycle activity remain tightly coupled in early adenoma cells. Adenocarcinoma cells are more flexible with respect to fuel source, enabling them to proliferate in nutrient-poor environments. Despite this plasticity, we identify asparagine (ASN) synthesis as a node of metabolic vulnerability in late-stage adenocarcinoma cells. We show that loss of asparagine synthetase (ASNS) blocks their proliferation, whereas early adenoma cells are largely resistant to ASN deprivation. Mechanistically, we show that late-stage adenocarcinoma cells are dependent on ASNS to support mTORC1 signalling and maximal glycolytic and oxidative capacity. Resistance to ASNS loss in early adenoma cells is likely due to a feedback loop, absent in late-stage cells, allowing them to sense and regulate ASN levels and supplement ASN by autophagy. Together, our study defines metabolic changes during CRC development and highlights ASN synthesis as a targetable metabolic vulnerability in later stage disease.
Mobile marketing interface layout attributes that affect user aesthetic preference: an eye-tracking study
Authors: Xiao Liang , Wang Shu 
Published: March 2022

PurposeThe rapid growth of m-commerce and mobile marketing has flooded the users with homogeneous contents that raise little user interest making the users' browsing pattern on these contents aimless free browsing. However, the interface that presents the mobile marketing contents triggers much user attention, especially the layout. Without significant usability defects, the layout poses influences on the user's aesthetic experience. Identifying the layout attributes that affect user aesthetic preference is critical to the design of mobile marketing interfaces since they influence users' interaction intention, cognitive process, and decision-making.Design/methodology/approachIn this paper, 6 layout attributes that quantify the aesthetic design of the interface layout and 3 eye-movement indicators that connect to human aesthetic preference were identified through literature research. An eye-tracking experiment measuring the 3 eye-movement indicators on 6 pairs of interface layout materials corresponding to the 6 layout attributes was conducted. The experiment was designed to mimic the free browsing context in mobile marketing. The materials were divided into Liked/Disliked preference groups according to the response of the subjects. Analysis of indicators on materials between the L/D groups shows that the attributes of balance, centricity, density, simplicity, and symmetry affect user aesthetic preferences.FindingsAnalysis of the attribute value levels shows that balance, centricity, and density are responsible for addressing users' aesthetic preferences for a disliked interface layout. The study suggests an attribute set for quantitatively optimizing the aesthetic design of mobile marketing system interfaces and provides evidence for the visual attention and cognitive process under the free browsing context.Originality/valueThe study contributes to the field both theoretically and practically: (1) it provides support for optimizing the interface layout of mobile marketing systems quantitatively from the aesthetic perspective. (2) It promotes the cognitive attention theory by providing evidence for the cognitive process of interacting with mobile marketing interfaces from the perspective of visual attention and cognitive fluency. (3) It expands the objects of visual perception from traditional or symbolic artworks (such as logos) to the abstract visual stimuli of interface layout. (4) It suggests an optimization tool of five quantification layout attributes for mobile marketing businesses and platforms to aesthetically improve their marketing interfaces to improve user experiences.
Interplay between servitization and platforms: a longitudinal case study
Authors: Fu Wenhui , Zhang Min , Zhao Xiande , Jia Fu 
Published: March 2022

PurposeThis paper aims to empirically explore the evolution of servitization and how platforms affect the transition between the stages of servitization.Design/methodology/approachThe authors conducted an in-depth case study of a Chinese manufacturer (i.e. Haier) using a longitudinal design. Three rounds of data collection were conducted between 2014 and 2020. The authors carried out 50 semi-structured interviews and 11 workshops to collect data from senior and middle managers of Haier and its business partners.FindingsThe authors found that Haier’s servitization journey includes three stages (i.e. product-oriented solution, integrated solution and smart connected solutions) that evolve in the target of the services and the digital components of the solutions. Haier has also developed three types of platforms (i.e. service platform, supply chain platform and platform ecosystem) to support the implementation of servitization. The empirical evidence reveals that platforms can address the complexities that emerged when Haier implements the different stages of servitization as well as enable Haier to transition from one stage of servitization to the next.Originality/valueThis study enhances the current understanding of the evolution of servitization and the roles of digital technologies in the transition between the stages of servitization. It also provides empirical evidence regarding how the platform approach enables the development of servitization. By clarifying the interplay between servitization and platforms, this study provides guidelines for managers on how to develop platforms to both advance and benefit from servitization.
On solving multi-objective fully quadratic fractional optimisation model with interactive FGP approach
Authors: Rani Namrata , Goyal Vandana , Gupta Deepak 
Published: March 2022

PurposeThe main motive behind framing this paper is to provide a compromised solution for trapezoidal fuzzy number–multi-objective fully quadratic fractional optimisation model (TrFN-MOFQFOM) by avoiding ambiguities and confusion of decision-makers (DMs). Many researchers have used Taylor's series and parametric approach to transform fractional objective function into non-fractional ones, but Taylor's series expansion is valid only up to a neighbourhood. To avoid these extra efforts, this article suggests a methodology in which numerator of objective function is optimised under the condition of optimising denominator.Design/methodology/approachThis paper suggests an efficient procedure to search for compromised solution of MOFQFOM with fuzzy coefficients using α-level set and FGP approach. Incomplete data in model is dealt with α-level set. Then after defuzzification, non-fractional models are built from fractional model to get optimal solution of every objective. Finally, the linear weighted sum of negative deviational variables is minimised to satisfy all objective functions up to maximum possible extent.FindingsOn applying suggested approach to the example given in end, the authors arrived at compromised solution having μO1(O1(x))=1 and μO2(O2(x))=0.71. The applied procedure requires less computational efforts and provides the preferred compromised solution.Originality/valueThis work has not been done previously by anyone. The idea being developed here of constructing non-fractional model by dealing numerators and denominators separately is completely new. 10; In the end, an algorithm, flowchart and numerical are also given to clarify the applicability of the suggested approach.