bluuebunny/crossref_metadata_2025_split huggingface dataset:
The trans-omics landscape of COVID-19
Authors: Wu Peng , Chen Dongsheng , Ding Wencheng , Wu Ping , Hou Hongyan , Bai Yong , Zhou Yuwen , Li Kezhen , Xiang Shunian , Liu Panhong , Ju Jia , Guo Ensong , Liu Jia , Yang Bin , Fan Junpeng , He Liang , Sun Ziyong , Feng Ling , Wang Jian , Wu Tangchun , Wang Hao , Cheng Jin , Xing Hui , Meng Yifan , Li Yongsheng , Zhang Yuanliang , Luo Hongbo , Xie Gang , Lan Xianmei , Tao Ye , Li Jiafeng , Yuan Hao , Huang Kang , Sun Wan , Qian Xiaobo , Li Zhichao , Huang Mingxi , Ding Peiwen , Wang Haoyu , Qiu Jiaying , Wang Feiyue , Wang Shiyou , Zhu Jiacheng , Ding Xiangning , Chai Chaochao , Liang Langchao , Wang Xiaoling , Luo Lihua , Sun Yuzhe , Yang Ying , Zhuang Zhenkun , Li Tao , Tian Lei , Zhang Shaoqiao , Zhu Linnan , Chang Ashley , Chen Lei , Wu Yiquan , Ma Xiaoyan , Chen Fang , Ren Yan , Xu Xun , Liu Siqi , Wang Jian , Yang Huanming , Wang Lin , Sun Chaoyang , Ma Ding , Jin Xin , Chen Gang 
Published: July 2021

AbstractThe outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.
Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice
Authors: Ehinger Yann , Zhang Ziyang , Phamluong Khanhky , Soneja Drishti , Shokat Kevan M. , Ron Dorit 
Published: July 2021

AbstractAlcohol Use Disorder (AUD) affects a large portion of the population. Unfortunately, efficacious medications to treat the disease are limited. Studies in rodents suggest that mTORC1 plays a crucial role in mechanisms underlying phenotypes such as heavy alcohol intake, habit, and relapse. Thus, mTORC1 inhibitors, which are used in the clinic, are promising therapeutic agents to treat AUD. However, chronic inhibition of mTORC1 in the periphery produces undesirable side effects, which limit their potential use for the treatment of AUD. To overcome these limitations, we designed a binary drug strategy in which male mice were treated with the mTORC1 inhibitor RapaLink-1 together with a small molecule (RapaBlock) to protect mTORC1 activity in the periphery. We show that whereas RapaLink-1 administration blocked mTORC1 activation in the liver, RapaBlock abolished the inhibitory action of Rapalink-1. RapaBlock also prevented the adverse side effects produced by chronic inhibition of mTORC1. Importantly, co-administration of RapaLink-1 and RapaBlock inhibited alcohol-dependent mTORC1 activation in the nucleus accumbens and attenuated alcohol seeking and drinking.
Cryo-EM structure of human Wntless in complex with Wnt3a
Authors: Zhong Qing , Zhao Yanyu , Ye Fangfei , Xiao Zaiyu , Huang Gaoxingyu , Xu Meng , Zhang Yuanyuan , Zhan Xiechao , Sun Ke , Wang Zhizhi , Cheng Shanshan , Feng Shan , Zhao Xiuxiu , Zhang Jizhong , Lu Peilong , Xu Wenqing , Zhou Qiang , Ma Dan 
Published: July 2021

AbstractWntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 Å resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A β-hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling.
Structural basis for genome packaging, retention, and ejection in human cytomegalovirus
Authors: Li Zhihai , Pang Jingjing , Dong Lili , Yu Xuekui 
Published: July 2021

AbstractHow the human cytomegalovirus (HCMV) genome—the largest among human herpesviruses—is packaged, retained, and ejected remains unclear. We present the in situ structures of the symmetry-mismatched portal and the capsid vertex-specific components (CVSCs) of HCMV. The 5-fold symmetric 10-helix anchor—uncommon among known portals—contacts the portal-encircling DNA, which is presumed to squeeze the portal as the genome packaging proceeds. We surmise that the 10-helix anchor dampens this action to delay the portal reaching a “head-full” packaging state, thus facilitating the large genome to be packaged. The 6-fold symmetric turret, latched via a coiled coil to a helix from a major capsid protein, supports the portal to retain the packaged genome. CVSCs at the penton vertices—presumed to increase inner capsid pressure—display a low stoichiometry, which would aid genome retention. We also demonstrate that the portal and capsid undergo conformational changes to facilitate genome ejection after viral cell entry.
Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional
Authors: Stancil Ian T. , Michalski Jacob E. , Davis-Hall Duncan , Chu Hong Wei , Park Jin-Ah , Magin Chelsea M. , Yang Ivana V. , Smith Bradford J. , Dobrinskikh Evgenia , Schwartz David A. 
Published: July 2021

AbstractThe airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of functionMUC5Bpromoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.
Hamiltonian simulation in the low-energy subspace
Authors: Şahinoğlu Burak , Somma Rolando D. 
Published: July 2021

AbstractWe study the problem of simulating the dynamics of spin systems when the initial state is supported on a subspace of low energy of a HamiltonianH. This is a central problem in physics with vast applications in many-body systems and beyond, where the interesting physics takes place in the low-energy sector. We analyze error bounds induced by product formulas that approximate the evolution operator and show that these bounds depend on an effective low-energy norm ofH. We find improvements over the best previous complexities of product formulas that apply to the general case, and these improvements are more significant for long evolution times that scale with the system size and/or small approximation errors. To obtain these improvements, we prove exponentially decaying upper bounds on the leakage to high-energy subspaces due to the product formula. Our results provide a path to a systematic study of Hamiltonian simulation at low energies, which will be required to push quantum simulation closer to reality.
Genetic diversity and population structure analysis of Lateolabrax maculatus from Chinese coastal waters using polymorphic microsatellite markers
Authors: Wang Wei , Ma Chunyan , Ouyang Longling , Chen Wei , Zhao Ming , Zhang Fengying , Fu Yin , Jiang Keji , Liu Zhiqiang , Zhang Heng , Ma Lingbo 
Published: July 2021

AbstractIn order to provide valuable guidelines for the conservation of germplasm ofLateolabrax maculatus, the genetic diversity and population structure analysis were evaluated for eight geographic populations along coastal regions of China, using 11 microsatellite DNA markers. The genetic parameters obtained showed that, eight populations can be clustered into two groups, the Northern group and the Southern group, concordant with their geographical positions. The UPGMA tree constructed according to the Nei’s genetic distance along with the structure analysis and discriminant analysis of principal component also supported this result. This might be explained by the geographic separation and the divergent environmental conditions among the populations. It's worth noting that, QD (Qingdao) population from northern area was assigned to the Southern group and showed a close genetic relationship and similar genetic constitution with the southern populations. We speculated that large scales of anthropogenic transportation of wild fries from QD populations to the southern aquaculture areas in history should be the primary cause. The populations from GY (Ganyu), RD (Rudong) and BH (Binhai) had higher genetic diversity and showed limited genetic exchange with other populations, indicating better conservation of the natural resources in these regions. All populations were indicated to have experienced bottleneck events in history.
Valorization of rare earth processing byproducts for agriculture usage
Authors: Hanafi Mohamed Musa , Azizi Parisa , Akinbola Sheu Tijani , Ismail Roslan , Sahibin Abdul Rahim , Wan Mohd Razi Idris , Ismail Aznan Fazli 
Published: July 2021

AbstractSandy texture soil, a major problem for agriculture requires structure and capacity improvements. However, utilization of soil conditioner may arrest this problem. This research was carried out to investigate the accumulated levels of metal ions and radionuclides in water, soil and plants following phosphogypsum organic (PG organic) added to a sandy soil for 23-month in 3 cropping seasons. The condition in the field was simulated in the laboratory using an open leaching column for 30-day under constant but different pH of leachant. More ions were released at pH < 4.6 and decreases greatly at pH > 5.6. The metal ions measured in the surface and borehole water, and soils were below the target values for respective standard raw drinking water. The metal ions did not accumulate in soil, plant and grain, and water as indicated by biological accumulation coefficients, contamination factors, I-geo index and pollution load index in a sandy soil that received the PG organic. Naturally occurring radionuclide concentrations, such as 226Ra, 228Ra, and 40K, in soil and plant tissue were found to be lower than the average value reported by several earlier studies. Under field condition the pH of water (i.e., rainfall) was greater than pH 5.6, thus renders PG organic became less soluble. There was no leaching of natural occurring radionuclides to the groundwater. Therefore, the application of PG organic to the studied soil had no impact on the soil, plants, and water and suitable as a soil conditioner in sandy texture soils.
Early life neonicotinoid exposure results in proximal benefits and ultimate carryover effects
Authors: Zgirski Thomas , Legagneux Pierre , Chastel Olivier , Regimbald Lyette , Prouteau Louise , Le Pogam Audrey , Budzinski Hélène , Love Oliver P. , Vézina François 
Published: July 2021

AbstractNeonicotinoids are insecticides widely used as seed treatments that appear to have multiple negative effects on birds at a diversity of biological scales. Adult birds exposed to a low dose of imidacloprid, one of the most commonly used neonicotinoids, presented reduced fat stores, delayed migration and potentially altered orientation. However, little is known on the effect of imidacloprid on birds growth rate despite studies that have documented disruptive effects of low imidacloprid doses on thyroid gland communication. We performed a$$2 \times 2$$2×2factorial design experiment in Zebra finches, in which nestling birds were exposed to a very low dose (0.205 mg kg body$$\hbox {mass}^{-1}$$mass-1) of imidacloprid combined with food restriction during posthatch development. During the early developmental period, imidacloprid exposure resulted in an improvement of body condition index in treated nestlings relative to controls. Imidacloprid also led to compensatory growth in food restricted nestlings. This early life neonicotinoid exposure also carried over to adult age, with exposed birds showing higher lean mass and basal metabolic rate than controls at ages of 90–800 days. This study presents the first evidence that very low-dose neonicotinoid exposure during early life can permanently alter adult phenotype in birds.
Analysis of long intergenic non-coding RNAs transcriptomic profiling in skeletal muscle growth during porcine embryonic development
Authors: Zhao Wenjuan , Li Zijing , Liu Quan , Xie Su , Li Mengxun , Wang Yuan , Li Changchun 
Published: July 2021

AbstractSkeletal muscle growth plays a critical role during porcine muscle development stages. Genome-wide transcriptome analysis reveals that long intergenic non-coding RNAs (lincRNAs) are implicated as crucial regulator involving in epigenetic regulation. However, comprehensive analysis of lincRNAs in embryonic muscle development stages remain still elusive. Here, we investigated the transcriptome profiles of Duroc embryonic muscle tissues from days 33, 65, and 90 of gestation using RNA-seq, and 228 putative lincRNAs were identified. Moreover, these lincRNAs exhibit the characteristics of shorter transcripts length, longer exons, less exon numbers and lower expression level compared with protein-coding transcripts. Expression profile analysis showed that a total of 120 lincRNAs and 2638 mRNAs were differentially expressed. In addition, we also performed quantitative trait locus (QTL) mapping analysis for differentially expressed lincRNAs (DE lincRNAs), 113 of 120 DE lincRNAs were localized on 2200 QTLs, we observed many QTLs involved in growth and meat quality traits. Furthermore, we predicted potential target genes of DE lincRNAs in cis or trans regulation. Gene ontology and pathway analysis reveals that potential targets of DE lincRNAs mostly were enriched in the processes and pathways related to tissue development, MAPK signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and insulin signaling pathway, which involved in skeletal muscle physiological functions. Based on cluster analysis, co-expression network analysis of DE lincRNAs and their potential target genes indicated that DE lincRNAs highly regulated protein-coding genes associated with skeletal muscle development. In this study, many of the DE lincRNAs may play essential roles in pig muscle growth and muscle mass. Our study provides crucial information for further exploring the molecular mechanisms of lincRNAs during skeletal muscle development.
Combined detection of peripheral blood VEGF and inflammation biomarkers to evaluate the clinical response and prognostic prediction of non-operative ESCC
Authors: Ma Yuanyuan , Su Xinyu , Li Xin , Zhi Xiaohui , Jiang Kan , Xia Jianhong , Li Hongliang , Yan Chen , Zhou Liqing 
Published: July 2021

AbstractAn association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC). Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA. VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS. The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool.
Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands
Authors: Serrano Ruben , Coch Christoph , Peters Christian , Hartmann Gunther , Wesch Daniela , Kabelitz Dieter 
Published: July 2021

AbstractHuman Vγ9Vδ2 T cells recognize pyrophosphates produced by microbes and transformed cells and play a role in anti-infective immunity and tumor surveillance. Toll-like receptors (TLR) are pattern recognition receptors in innate immune cells which sense microbial structures including nucleic acids. Given that γδ T cells are in clinical development for application in cellular cancer immunotherapy and TLR ligands have potent adjuvant activity, we investigated the co-stimulatory role of selected TLR ligands in γδ T-cell activation. Here we have used recently described RNA ligands for TLR7 and TLR8 together with Vγ9Vδ2 T-cell specific pyrophosphate antigens to analyze the rapid cytokine induction in Vδ2 T cells as well as the accessory cell requirements. While TLR8- as well as TLR7/8-specific RNA did not induce IFN-γ in Vδ2 T cells on their own, they provided strong co-stimulation for Vδ2 T cells within peripheral blood mononuclear cells in the presence of additional T-cell receptor activation. In contrast, TLR7 ligands were ineffective. Purified γδ T cells did not directly respond to TLR8 co-stimulation but required the presence of monocytes. Further experiments revealed a critical role of IL-1β and IL-18, and to a slightly lesser extent of IL-12p70, in the co-stimulation of Vδ2 T cells by TLR8 and TLR7/8 RNA ligands. Results of intracellular cytokine expression were validated by ELISA analysis of cytokines in cell culture supernatants. The cell context-dependent adjuvant activity of TLR8 and TLR7/8 RNA ligands described here might be important for the future optimization of γδ T-cell based cancer immunotherapy.
A data-driven approach to modeling cancer cell mechanics during microcirculatory transport
Authors: Balogh Peter , Gounley John , Roychowdhury Sayan , Randles Amanda 
Published: July 2021

AbstractIn order to understand the effect of cellular level features on the transport of circulating cancer cells in the microcirculation, there has been an increasing reliance on high-resolution in silico models. Accurate simulation of cancer cells flowing with blood cells requires resolving cellular-scale interactions in 3D, which is a significant computational undertaking warranting a cancer cell model that is both computationally efficient yet sufficiently complex to capture relevant behavior. Given that the characteristics of metastatic spread are known to depend on cancer type, it is crucial to account for mechanistic behavior representative of a specific cancer’s cells. To address this gap, in the present work we develop and validate a means by which an efficient and popular membrane model-based approach can be used to simulate deformable cancer cells and reproduce experimental data from specific cell lines. Here, cells are modeled using the immersed boundary method (IBM) within a lattice Boltzmann method (LBM) fluid solver, and the finite element method (FEM) is used to model cell membrane resistance to deformation. Through detailed comparisons with experiments, we (i) validate this model to represent cancer cells undergoing large deformation, (ii) outline a systematic approach to parameterize different cell lines to optimally fit experimental data over a range of deformations, and (iii) provide new insight into nucleated vs. non-nucleated cell models and their ability to match experiments. While many works have used the membrane-model based method employed here to model generic cancer cells, no quantitative comparisons with experiments exist in the literature for specific cell lines undergoing large deformation. Here, we describe a phenomenological, data-driven approach that can not only yield good agreement for large deformations, but explicitly detail how it can be used to represent different cancer cell lines. This model is readily incorporated into cell-resolved hemodynamic transport simulations, and thus offers significant potential to complement experiments towards providing new insights into various aspects of cancer progression.