bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human genetic basis of coronavirus disease 2019
Authors: Deng Hao , Yan Xue , Yuan Lamei 
Published: September 2021

AbstractCoronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in considerable morbidity and mortality worldwide. COVID-19 incidence, severity, and mortality rates differ greatly between populations, genders, ABO blood groups, human leukocyte antigen (HLA) genotypes, ethnic groups, and geographic backgrounds. This highly heterogeneous SARS-CoV-2 infection is multifactorial. Host genetic factors such as variants in the angiotensin-converting enzyme gene (ACE), the angiotensin-converting enzyme 2 gene (ACE2), the transmembrane protease serine 2 gene (TMPRSS2), along with HLA genotype, and ABO blood group help to explain individual susceptibility, severity, and outcomes of COVID-19. This review is focused on COVID-19 clinical and viral characteristics, pathogenesis, and genetic findings, with particular attention on genetic diversity and variants. The human genetic basis could provide scientific bases for disease prediction and targeted therapy to address the COVID-19 scourge.
Targeting the Lnc-OPHN1-5/androgen receptor/hnRNPA1 complex increases Enzalutamide sensitivity to better suppress prostate cancer progression
Authors: Zhang Meng , Sun Yin , Huang Chi-Ping , Luo Jie , Zhang Li , Meng Jialin , Liang Chaozhao , Chang Chawnshang 
Published: September 2021

AbstractLong non-coding RNAs (lncRNAs) have been found to play critical roles in regulating gene expression, but their function in translational control is poorly understood. We found lnc-OPHN1-5, which lies close to the androgen receptor (AR) gene on chromosome X, increased prostate cancer (PCa) Enzalutamide (Enz) sensitivity via decreasing AR protein expression and associated activity. Mechanism dissection revealed that lnc-OPHN1-5 interacted with AR-mRNA to minimize its interaction with the RNA binding protein (RBP) hnRNPA1. Suppressing lnc-OPHN1-5 expression promoted the interaction between AR-mRNA and hnRNPA1, followed by an increase of ribosome association with AR-mRNA and translation. This effect was reversed by increasing lnc-OPHN1-5 expression. Consistently, the in vivo mice model confirmed that knocking down lnc-OPHN1-5 expression in tumors significantly increased the tumor formation rate and AR protein expression compared with the control group. Furthermore, knocking down hnRNPA1 blocked/reversed shlnc-OPHN1-5-increased AR protein expression and re-sensitized cells to Enz treatment efficacy. Evidence from Enz-resistant cell lines, patient-derived xenograft (PDX) models, clinical samples, and a human PCa study accordantly suggested that patients with low expression of lnc-OPHN1-5 likely have unfavorable prognoses and probably are less sensitive to Enz treatment. In summary, targeting this newly identified lnc-OPHN1-5/AR/hnRNPA1 complex may help develop novel therapies to increase Enz treatment sensitivity for suppressing the PCa at an advanced stage.
7,8-dihydroxyflavone ameliorates motor deficits via regulating autophagy in MPTP-induced mouse model of Parkinson’s disease
Authors: Zuo Li , Dai Chunfang , Yi Lilin , Dong Zhifang 
Published: September 2021

AbstractParkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra and diminished dopamine content in the striatum. Recent reports show that 7,8-dihydroxyflavone (DHF), a TrkB agonist, attenuates the α-synuclein deposition and ameliorates motor deficits. However, the underlying mechanism is unclear. In this study, we investigated whether autophagy is involved in the clearance of α-synuclein and the signaling pathway through which DHF exerts therapeutic effects. We found that the administration of DHF (5 mg/kg/day, i.p.) prevented the loss of dopaminergic neurons and improved motor functions in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, whereas these protective effects of DHF were completely blocked by autophagy inhibitor chloroquine (CQ). Further in vitro studies showed that autophagy was inhibited in N2A cells treated with 1-methyl-4-phenylpyridinium (MPP+), as reflected by a significant decrease in the expressions of autophagy marker proteins (Beclin1 and LC3II) and an increase in the expression of autophagic flux marker p62. DHF restored the impaired autophagy to control level in MPP+-treated N2A cells by inhibiting the ERK-LKB1-AMPK signaling pathway. Taken together, these results demonstrate that DHF exerts therapeutic effects in MPTP/MPP+-induced neurotoxicity by inhibiting the ERK-LKB1-AMPK signaling pathway and subsequently improving impaired autophagy.
Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer
Authors: Lu Jiawei , Xu Ying , Xie Wenjie , Tang Yinbing , Zhang Heteng , Wang Beibei , Mao Ji , Rui Tao , Jiang Pengcheng , Zhang Wenbo 
Published: September 2021

AbstractThe long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/β-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/β-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/β-catenin signaling could effectively abolish the activation of Wnt/β-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/β-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.
Multi-level inhibition of coronavirus replication by chemical ER stress
Authors: Shaban Mohammed Samer , Müller Christin , Mayr-Buro Christin , Weiser Hendrik , Meier-Soelch Johanna , Albert Benadict Vincent , Weber Axel , Linne Uwe , Hain Torsten , Babayev Ilya , Karl Nadja , Hofmann Nina , Becker Stephan , Herold Susanne , Schmitz M. Lienhard , Ziebuhr John , Kracht Michael 
Published: September 2021

AbstractCoronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. The ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types including primary differentiated human bronchial epithelial cells, (partially) reverses the virus-induced translational shut-down, improves viability of infected cells and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. Proteome-wide analyses revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including essential (HERPUD1) or novel (UBA6 and ZNF622) factors of ER quality control, and ER-associated protein degradation complexes. Additionally, thapsigargin blocks the CoV-induced selective autophagic flux involving p62/SQSTM1. The data show that thapsigargin hits several central mechanisms required for CoV replication, suggesting that this compound (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs.
An electron-deficient carbon current collector for anode-free Li-metal batteries
Authors: Kwon Hyeokjin , Lee Ju-Hyuk , Roh Youngil , Baek Jaewon , Shin Dong Jae , Yoon Jong Keon , Ha Hoe Jin , Kim Je Young , Kim Hee-Tak 
Published: September 2021

AbstractThe long-term cycling of anode-free Li-metal cells (i.e., cells where the negative electrode is in situ formed by electrodeposition on an electronically conductive matrix of lithium sourced from the positive electrode) using a liquid electrolyte is affected by the formation of an inhomogeneous solid electrolyte interphase (SEI) on the current collector and irregular Li deposition. To circumvent these issues, we report an atomically defective carbon current collector where multivacancy defects induce homogeneous SEI formation on the current collector and uniform Li nucleation and growth to obtain a dense Li morphology. Via simulations and experimental measurements and analyses, we demonstrate the beneficial effect of electron deficiency on the Li hosting behavior of the carbon current collector. Furthermore, we report the results of testing anode-free coin cells comprising a multivacancy defective carbon current collector, a LixNi0.8Co0.1Mn0.1-based cathode and a nonaqueous Li-containing electrolyte solution. These cells retain 90% of their initial capacity for over 50 cycles under lean electrolyte conditions.
Modular ketal-linked prodrugs and biomaterials enabled by organocatalytic transisopropenylation of alcohols
Authors: Yu Na , Xu Yang , Liu Tao , Zhong Haiping , Xu Zunkai , Ji Tianjiao , Zou Hui , Mu Jingqing , Chen Ziqi , Liang Xing-Jie , Shi Linqi , Kohane Daniel S. , Guo Shutao 
Published: September 2021

AbstractIsopropenyl ethers are critical intermediates for accessing medicinally valuable ketal-based prodrugs and biomaterials, but traditional approaches for the synthesis of isopropenyl ethers suffer from poor functional group compatibility and harsh reaction conditions. Here, we develop an organocatalytic transisopropenylation approach to solve these challenges, enabling the synthesis of isopropenyl ethers from various hydroxyl-group-containing small-molecule drugs, polymers, and functional building blocks. The method provides a straightforward and versatile synthesis of isopropenyl ethers, features excellent tolerance of diverse functional groups, applies to a wide range of substrates, and allows scalable synthesis. The development of this organocatalytic transisopropenylation approach enables access to modular preparation of various acid-sensitive ketal-linked prodrugs and functionalized ketalated biomaterials. We expect our syntheses and transformations of isopropenyl ethers will find utility in several diverse fields, including medicinal chemistry, drug delivery, and biomaterials.
A novel nairovirus associated with acute febrile illness in Hokkaido, Japan
Authors: Kodama Fumihiro , Yamaguchi Hiroki , Park Eunsil , Tatemoto Kango , Sashika Mariko , Nakao Ryo , Terauchi Yurino , Mizuma Keita , Orba Yasuko , Kariwa Hiroaki , Hagiwara Katsuro , Okazaki Katsunori , Goto Akiko , Komagome Rika , Miyoshi Masahiro , Ito Takuya , Yamano Kimiaki , Yoshii Kentaro , Funaki Chiaki , Ishizuka Mariko , Shigeno Asako , Itakura Yukari , Bell-Sakyi Lesley , Edagawa Shunji , Nagasaka Atsushi , Sakoda Yoshihiro , Sawa Hirofumi , Maeda Ken , Saijo Masayuki , Matsuno Keita 
Published: September 2021

AbstractThe increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014–2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan.
Local-electrostatics-induced oxygen octahedral distortion in perovskite oxides and insight into the structure of Ruddlesden–Popper phases
Authors: Hong Youngjae , Byeon Pilgyu , Bak Jumi , Heo Yoon , Kim Hye-Sung , Bae Hyung Bin , Chung Sung-Yoon 
Published: September 2021

AbstractAs the physical properties of ABX3 perovskite-based oxides strongly depend on the geometry of oxygen octahedra containing transition-metal cations, precise identification of the distortion, tilt, and rotation of the octahedra is an essential step toward understanding the structure–property correlation. Here we discover an important electrostatic origin responsible for remarkable Jahn–Teller-type tetragonal distortion of oxygen octahedra during atomic-level direct observation of two-dimensional [AX] interleaved shear faults in five different perovskite-type materials, SrTiO3, BaCeO3, LaCoO3, LaNiO3, and CsPbBr3. When the [AX] sublayer has a net charge, for example [LaO]+ in LaCoO3 and LaNiO3, substantial tetragonal elongation of oxygen octahedra at the fault plane is observed and this screens the strong repulsion between the consecutive [LaO]+ layers. Moreover, our findings on the distortion induced by local charge are identified to be a general structural feature in lanthanide-based An + 1BnX3n + 1-type Ruddlesden–Popper (RP) oxides with charged [LnO]+ (Ln = La, Pr, Nd, Eu, and Gd) sublayers, among more than 80 RP oxides and halides with high symmetry. The present study thus demonstrates that the local uneven electrostatics is a crucial factor significantly affecting the crystal structure of complex oxides.
Dissemination of Mycobacterium abscessus via global transmission networks
Authors: Ruis Christopher , Bryant Josephine M. , Bell Scott C. , Thomson Rachel , Davidson Rebecca M. , Hasan Nabeeh A. , van Ingen Jakko , Strong Michael , Floto R. Andres , Parkhill Julian 
Published: September 2021

AbstractMycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission.
ValLAI_Crop, a validation dataset for coarse-resolution satellite LAI products over Chinese cropland
Authors: Song Bowen , Liu Liangyun , Du Shanshan , Zhang Xiao , Chen Xidong , Zhang Helin 
Published: September 2021

AbstractNumerous validation efforts have been conducted over the last decade to assess the accuracy of global leaf area index (LAI) products. However, such efforts continue to face obstacles due to the lack of sufficient high-quality field measurements. In this study, a fine-resolution LAI dataset consisting of 80 reference maps was generated during 2003–2017. The direct destructive method was used to measure the field LAI, and fine-resolution LAI images were derived from Landsat images using semiempirical inversion models. Eighty reference LAI maps, each with an area of 3 km × 3 km and a percentage of cropland larger than 75%, were selected as the fine-resolution validation dataset. The uncertainty associated with the spatial scale effect was also provided. Ultimately, the fine-resolution reference LAI dataset was used to validate the Moderate Resolution Imaging Spectroradiometer (MODIS) LAI product. The results indicate that the fine-resolution reference LAI dataset builds a bridge to link small sampling plots and coarse-resolution pixels, which is extremely important in validating coarse-resolution LAI products.
Multiple strain analysis of Streptomyces species from Philippine marine sediments reveals intraspecies heterogeneity in antibiotic activities
Authors: Tenebro Chuckcris P. , Trono Dana Joanne Von L. , Vicera Carmela Vannette B. , Sabido Edna M. , Ysulat Jovito A. , Macaspac Aaron Joseph M. , Tampus Kimberly A. , Fabrigar Trisha Alexis P. , Saludes Jonel P. , Dalisay Doralyn S. 
Published: September 2021

AbstractThe marine ecosystem has become the hotspot for finding antibiotic-producing actinomycetes across the globe. Although marine-derived actinomycetes display strain-level genomic and chemodiversity, it is unclear whether functional traits, i.e., antibiotic activity, vary in near-identical Streptomyces species. Here, we report culture-dependent isolation, antibiotic activity, phylogeny, biodiversity, abundance, and distribution of Streptomyces isolated from marine sediments across the west-central Philippines. Out of 2212 marine sediment-derived actinomycete strains isolated from 11 geographical sites, 92 strains exhibited antibacterial activities against multidrug-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The 16S rRNA and rpoB gene sequence analyses confirmed that antibiotic-producing strains belong to the genus Streptomyces, highlighting Streptomyces parvulus as the most dominant species and three possible new species. Antibiotic-producing Streptomyces strains were highly diverse in Southern Antique, and species diversity increase with marine sediment depth. Multiple strains with near-identical 16S rRNA and rpoB gene sequences displayed varying strength of antibiotic activities. The genotyping of PKS and NRPS genes revealed that closely related antibiotic-producing strains have similar BGC domains supported by their close phylogenetic proximity. These findings collectively suggest Streptomyces' intraspecies adaptive characteristics in distinct ecological niches that resulted in outcompeting other bacteria through differential antibiotic production.
Association mining based approach to analyze COVID-19 response and case growth in the United States
Authors: Katragadda Satya , Gottumukkala Raju , Bhupatiraju Ravi Teja , Kamal Azmyin Md. , Raghavan Vijay , Chu Henry , Kolluru Ramesh , Ashkar Ziad 
Published: September 2021

AbstractContaining the COVID-19 pandemic while balancing the economy has proven to be quite a challenge for the world. We still have limited understanding of which combination of policies have been most effective in flattening the curve; given the challenges of the dynamic and evolving nature of the pandemic, lack of quality data etc. This paper introduces a novel data mining-based approach to understand the effects of different non-pharmaceutical interventions in containing the COVID-19 infection rate. We used the association rule mining approach to perform descriptive data mining on publicly available data for 50 states in the United States to understand the similarity and differences among various policies and underlying conditions that led to transitions between different infection growth curve phases. We used a multi-peak logistic growth model to label the different phases of infection growth curve. The common trends in the data were analyzed with respect to lockdowns, face mask mandates, mobility, and infection growth. We observed that face mask mandates combined with mobility reduction through moderate stay-at-home orders were most effective in reducing the number of COVID-19 cases across various states.
Higher ultraviolet radiation during early life is associated with lower risk of childhood type 1 diabetes among boys
Authors: Miller Kate M. , Hart Prue H. , Lucas Robyn M. , Davis Elizabeth A. , de Klerk Nicholas H. 
Published: September 2021

AbstractPopulation-level ecological studies show type 1 diabetes incidence is inversely correlated with ambient ultraviolet radiation (UVR) levels. We conducted a nested case–control study using administrative datasets to test this association at the individual level. Cases (n = 1819) were children born in Western Australia (WA) from 1980–2014, diagnosed with type 1 diabetes at ≤ 16 years. Controls (n = 27,259) were randomly selected from all live births in WA, matched to cases by sex and date of birth. Total ambient erythemal ultraviolet radiation (UVR) doses for each trimester of pregnancy and first year of life were estimated for each individual, using daily NASA satellite data that were date- and geographically-specific. Conditional logistic regression tested the association between UVR dose and case–control status. Type 1 diabetes risk was 42% lower in boys of mothers with third-trimester UVR dose in the highest (compared to the lowest) quartile (p = 0.04). Higher UVR in the first year of life was associated with lower type 1 diabetes risk among boys (p = 0.01). UVR dose was not associated with type 1 diabetes risk in girls. Higher UVR in late pregnancy and early life appear to interact with sex-specific factors to lower type 1 diabetes risk among boys in Western Australia.
Assessment of the effectiveness of the EUROFORGEN NAME and Precision ID Ancestry panel markers for ancestry investigations
Authors: Truelsen D. , Tvedebrink T. , Mogensen H. S. , Farzad M. S. , Shan M. A. , Morling N. , Pereira V. , Børsting C. 
Published: September 2021

AbstractThe EUROFORGEN NAME panel is a regional ancestry panel designed to differentiate individuals from the Middle East, North Africa, and Europe. The first version of the panel was developed for the MassARRAY system and included 111 SNPs. Here, a custom AmpliSeq EUROFORGEN NAME panel with 102 of the original 111 loci was used to sequence 1098 individuals from 14 populations from Europe, the Middle East, North Africa, North-East Africa, and South-Central Asia. These samples were also sequenced with a global ancestry panel, the Precision ID Ancestry Panel. The GenoGeographer software was used to assign the AIM profiles to reference populations and calculate the weight of the evidence as likelihood ratios. The combination of the EUROFORGEN NAME and Precision ID Ancestry panels led to fewer ambiguous assignments, especially for individuals from the Middle East and South-Central Asia. The likelihood ratios showed that North African individuals could be separated from European and Middle Eastern individuals using the Precision ID Ancestry Panel. The separation improved with the addition of the EUROFORGEN NAME panel. The analyses also showed that the separation of Middle Eastern populations from European and South-Central Asian populations was challenging even when both panels were applied.