bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forecasting Abrupt Depletion of Dissolved Oxygen in Urban Streams Using Discontinuously Measured Hourly Time‐Series Data
Authors: Kim Young Woo , Kim TaeHo , Shin Jihoon , Go ByeongGeon , Lee Mokyoung , Lee JinHyo , Koo Jayong , Cho Kyung Hwa , Cha YoonKyung 
Published: March 2021

AbstractDepletion of dissolved oxygen (DO) is a major cause of fish kills in urban streams. Although forecasting short‐term DO concentrations in streams prior to hypoxic events is necessary, such efforts have been rarely made. In this study, 24‐h forecasting models were developed for DO concentrations in three urban streams of South Korea. To forecast the DO concentrations at the outlet sites, which coincide with fish kill hot spot areas, water quality parameters at the lower reaches and hydrometeorological parameters were used as input variables. The monitoring data were measured hourly between 2017 and 2018 and divided into training and test sets at a ratio of 8:2. Tenfold cross validation was performed for hyperparameter optimization. Due to the dynamic characteristics of DO concentrations and the discontinuity in time‐series data, a long short‐term memory (LSTM) neural network modeling approach was selected. Overall, a high degree of accuracy was recorded for all study streams. Although hypoxic events were forecast with lower accuracy, the timing and magnitude of abrupt DO depletion were well captured. Water temperature and DO concentrations at the lower reaches and 24‐h cumulative precipitation were important variables for forecasting DO concentrations at all stream outlets. In particular, the importance of cumulative precipitation across all streams indicated that the effects of nonpoint sources were critical in depleting DO in urban streams. Monitoring of both lower reaches and outlets in conjunction with a variable importance analysis enhanced interpretability of the LSTM model outputs. This study improves our understanding of precursors of hypoxic events in urban streams.
Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging
Authors: Wang Qian , Nie Lulingxiao , Zhao Pengfei , Zhou Xinyi , Ding Yi , Chen Qianming , Wang Qi 
Published: March 2021

AbstractHyperglycemia induces chronic low-grade inflammation (inflammaging), which is a newly identified contributor to diabetes-related tissue lesions, including the inflammatory bone loss in periodontitis. It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype (SASP). Macrophage is a key SASP-spreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment. Using a transgenic diabetic model (BLKS/J-Leprdb/leprdb mice) we identified striking senescence of the periodontium in young (18-wk)-diabetic mice accompanied by amassed p16+-macrophages and enhanced early SASP response. Exposed to high glucose in vitro, bone marrow-derived macrophage (BMDM) revealed a strong GLUT1 mRNA response driving the elevated-glucose uptake. GLUT1 is a representative and facilitative glucose transporter in macrophages with potential roles in hyperglycemia-induced inflammation. In this study, both GLUT1 and the downstream GTPase Rheb expression upregulated in the gingiva of diabetic mice with impaired condition. Furthermore, SASP release and p16/p21 signaling were proven to be triggered by mTOR phosphorylation in BMDM and antagonized by restricting glucose uptake in GLUT1−/− BMDM. Taken together, our findings suggest that elevated-GLUT1 sensor responded to high glucose is important for macrophage senescence and SASP response, generated as a result of hyperglycemia, and it is a potential molecular mechanism for the exacerbation of periodontitis in diabetes.
The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum
Authors: Wang Fei , Wang Qianqian , Liu Baowei , Mei Lisheng , Ma Sisi , Wang Shujuan , Wang Ruoyu , Zhang Yan , Niu Chaoshi , Xiong Zhiqi , Zheng Yong , Zhang Zhi , Shi Juan , Song Xiaoyuan 
Published: March 2021

AbstractThe brain is known to express many long noncoding RNAs (lncRNAs); however, whether and how these lncRNAs function in modulating synaptic stability remains unclear. Here, we report a cerebellum highly expressed lncRNA, Synage, regulating synaptic stability via at least two mechanisms. One is through the function of Synage as a sponge for the microRNA miR-325-3p, to regulate expression of the known cerebellar synapse organizer Cbln1. The other function is to serve as a scaffold for organizing the assembly of the LRP1-HSP90AA1-PSD-95 complex in PF-PC synapses. Although somewhat divergent in its mature mRNA sequence, the locus encoding Synage is positioned adjacent to the Cbln1 loci in mouse, rhesus macaque, and human, and Synage is highly expressed in the cerebella of all three species. Synage deletion causes a full-spectrum cerebellar ablation phenotype that proceeds from cerebellar atrophy, through neuron loss, on to synapse density reduction, synaptic vesicle loss, and finally to a reduction in synaptic activity during cerebellar development; these deficits are accompanied by motor dysfunction in adult mice, which can be rescued by AAV-mediated Synage overexpression from birth. Thus, our study demonstrates roles for the lncRNA Synage in regulating synaptic stability and function during cerebellar development.
Inhibition of HECT E3 ligases as potential therapy for COVID-19
Authors: Novelli Giuseppe , Liu Jing , Biancolella Michela , Alonzi Tonino , Novelli Antonio , Patten J. J. , Cocciadiferro Dario , Agolini Emanuele , Colona Vito Luigi , Rizzacasa Barbara , Giannini Rosalinda , Bigio Benedetta , Goletti Delia , Capobianchi Maria Rosaria , Grelli Sandro , Mann Justin , McKee Trevor D. , Cheng Ke , Amanat Fatima , Krammer Florian , Guarracino Andrea , Pepe Gerardo , Tomino Carlo , Tandjaoui-Lambiotte Yacine , Uzunhan Yurdagul , Tubiana Sarah , Ghosn Jade ,   COVID Human Genetic Effort,   French COVID Cohort Study Group,   CoV-Contact Cohort, Notarangelo Luigi D. , Su Helen C. , Abel Laurent , Cobat Aurélie , Elhanan Gai , Grzymski Joseph J. , Latini Andrea , Sidhu Sachdev S. , Jain Suresh , Davey Robert A. , Casanova Jean-Laurent , Wei Wenyi , Pandolfi Pier Paolo 
Published: March 2021

AbstractSARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.
A vaccine targeting mutant IDH1 in newly diagnosed glioma
Authors: Platten Michael , Bunse Lukas , Wick Antje , Bunse Theresa , Le Cornet Lucian , Harting Inga , Sahm Felix , Sanghvi Khwab , Tan Chin Leng , Poschke Isabel , Green Edward , Justesen Sune , Behrens Geoffrey A. , Breckwoldt Michael O. , Freitag Angelika , Rother Lisa-Marie , Schmitt Anita , Schnell Oliver , Hense Jörg , Misch Martin , Krex Dietmar , Stevanovic Stefan , Tabatabai Ghazaleh , Steinbach Joachim P. , Bendszus Martin , von Deimling Andreas , Schmitt Michael , Wick Wolfgang 
Published: March 2021

AbstractMutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1–3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H)+ tumours in syngeneic MHC-humanized mice4,6–8. Here we describe a multicentre, single-arm, open-label, first-in-humans phase I trial that we carried out in 33 patients with newly diagnosed World Health Organization grade 3 and 4 IDH1(R132H)+ astrocytomas (Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), ClinicalTrials.gov identifier NCT02454634). The trial met its primary safety endpoint, with vaccine-related adverse events restricted to grade 1. Vaccine-induced immune responses were observed in 93.3% of patients across multiple MHC alleles. Three-year progression-free and death-free rates were 0.63 and 0.84, respectively. Patients with immune responses showed a two-year progression-free rate of 0.82. Two patients without an immune response showed tumour progression within two years of first diagnosis. A mutation-specificity score that incorporates the duration and level of vaccine-induced IDH1(R132H)-specific T cell responses was associated with intratumoral presentation of the IDH1(R132H) neoantigen in pre-treatment tumour tissue. There was a high frequency of pseudoprogression, which indicates intratumoral inflammatory reactions. Pseudoprogression was associated with increased vaccine-induced peripheral T cell responses. Combined single-cell RNA and T cell receptor sequencing showed that tumour-infiltrating CD40LG+ and CXCL13+ T helper cell clusters in a patient with pseudoprogression were dominated by a single IDH1(R132H)-reactive T cell receptor.
Risk compensation after HIV-1 vaccination may accelerate viral adaptation and reduce cost-effectiveness: a modeling study
Authors: Peebles Kathryn , Mittler John E. , Goodreau Steven M. , Murphy James T. , Reid Molly C. , Abernethy Neil , Gottlieb Geoffrey S. , Barnabas Ruanne V. , Herbeck Joshua T. 
Published: March 2021

AbstractPathogen populations can evolve in response to selective pressure from vaccine-induced immune responses. For HIV, models predict that viral adaptation, either via strain replacement or selection on de novo mutation, may rapidly reduce the effectiveness of an HIV vaccine. We hypothesized that behavioral risk compensation after vaccination may accelerate the transmission of vaccine resistant strains, increasing the rate of viral adaptation and leading to a more rapid decline in vaccine effectiveness. To test our hypothesis, we modeled: (a) the impact of risk compensation on rates of HIV adaptation via strain replacement in response to a partially effective vaccine; and (b) the combined impact of risk compensation and viral adaptation on vaccine-mediated epidemic control. We used an agent-based epidemic model that was calibrated to HIV-1 trends in South Africa, and includes demographics, sexual network structure and behavior, and within-host disease dynamics. Our model predicts that risk compensation can increase the rate of HIV viral adaptation in response to a vaccine. In combination, risk compensation and viral adaptation can, under certain scenarios, reverse initial declines in prevalence due to vaccination, and result in HIV prevalence at 15 years equal to or greater than prevalence without a vaccine.
Measuring spatial co-occurrences of species potentially involved in Leishmania transmission cycles through a predictive and fieldwork approach
Authors: López Marla , Erazo Diana , Hoyos Juliana , León Cielo , Fuya Patricia , Lugo Ligia , Cordovez Juan Manuel , González Camila 
Published: March 2021

AbstractThe Leishmaniases are a group of neglected tropical diseases caused by different species of the protozoan parasiteLeishmania, transmitted to its mammalian hosts by the bites of several species of female Phlebotominae sand flies. Many factors have contributed to shifts in the disease distribution and eco epidemiological outcomes, resulting in the emergence of Cutaneous Leishmaniasis outbreaks and the incrimination of vectors in unreported regions. New research development is vital for establishing the new paradigms of the present transmission cycles, hoping to facilitate new control strategies to reduce parasite transmission. Hereafter, this work aims to model and infer the current transmission cycles of Cutaneous Leishmaniasis in Colombia defined by vector and mammal species distributed and interacting in the different regions and validate them by performing sand fly and mammal collections. Vector-host co-occurrences were computed considering five ecoregions of the Colombian territory defined by the World Wide Fund for Nature (WWF) and downloaded from The Nature Conservancy TNC Maps website. Four validation sites were selected based on Cutaneous Leishmaniasis prevalence reports. Sand flies and mammals captured in the field were processed, and species were defined using conventional taxonomic guidelines. Detection of infection byLeishmaniawas performed to identify transmission cycles in the selected areas. This study uses predictive models based on available information from international gazetteers and fieldwork to confirm sand fly and mammalian species' sustainingLeishmaniatransmission cycles. Our results show an uneven distribution of mammal samples in Colombia, possibly due to sampling bias, since only two departments contributed 50% of the available samples. Bats were the vertebrates with the highest score values, suggesting substantial spatial overlap with sand flies than the rest of the vertebrates evaluated. Fieldwork allowed identifying three circulatingLeishmaniaspecies, isolated from three sand fly species. In the Montane Forest ecosystem, one small marsupial,Gracilinanus marica, was found infected withLeishmania panamensis, constituting the first record of this species infected withLeishmania. In the same locality, an infected sand fly,Pintomyia pia,was found. The overall results could support the understanding of the current transmission cycles of Leishmaniasis in Colombia.
Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients
Authors: Li Yang , Jiang Yongzhong , Zhang Yi , Li Naizhe , Yin Qiangling , Liu Linlin , Lv Xin , Liu Yan , Li Aqian , Fang Bin , Li Jiajia , Ye Hengping , Yang Gang , Cui Xiaoxian , Liu Yang , Qu Yuanyuan , Li Chuan , Li Jiandong , Li Dexin , Gai Zhongtao , Wang Shiwen , Zhan Faxian , Liang Mifang 
Published: March 2021

AbstractHigh rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.
Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals
Authors: Martínez-Magaña José Jaime , Genis-Mendoza Alma Delia , Villatoro Velázquez Jorge Ameth , Bustos-Gamiño Marycarmen , Juárez-Rojop Isela Esther , Tovilla-Zarate Carlos Alfonso , Sarmiento Emmanuel , Saucedo Erasmo , Rodríguez-Mayoral Oscar , Fleiz-Bautista Clara , Camarena Beatriz , Aguilar Alejandro , Gonzalez-Castro Thelma Beatriz , Medina-Mora María Elena , Nicolini Humberto 
Published: March 2021

AbstractThe combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e−05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.
Genome-wide association study and gene network analyses reveal potential candidate genes for high night temperature tolerance in rice
Authors: Bheemanahalli Raju , Knight Montana , Quinones Cherryl , Doherty Colleen J. , Jagadish S. V. Krishna 
Published: March 2021

AbstractHigh night temperatures (HNT) are shown to significantly reduce rice (Oryza sativa L.) yield and quality. A better understanding of the genetic architecture of HNT tolerance will help rice breeders to develop varieties adapted to future warmer climates. In this study, a diverse indica rice panel displayed a wide range of phenotypic variability in yield and quality traits under control night (24 °C) and higher night (29 °C) temperatures. Genome-wide association analysis revealed 38 genetic loci associated across treatments (18 for control and 20 for HNT). Nineteen loci were detected with the relative changes in the traits between control and HNT. Positive phenotypic correlations and co-located genetic loci with previously cloned grain size genes revealed common genetic regulation between control and HNT, particularly grain size. Network-based predictive models prioritized 20 causal genes at the genetic loci based on known gene/s expression under HNT in rice. Our study provides important insights for future candidate gene validation and molecular marker development to enhance HNT tolerance in rice. Integrated physiological, genomic, and gene network-informed approaches indicate that the candidate genes for stay-green trait may be relevant to minimizing HNT-induced yield and quality losses during grain filling in rice by optimizing source-sink relationships.
Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement in cell organelles
Authors: Hahn Marc Benjamin , Zutta Villate Julián Mateo 
Published: March 2021

AbstractDose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined. Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. To estimate these effects, particle scattering simulations are applied. In general, different approaches for modeling the AuNP and their distribution within the cell are possible. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. These models are applicable to simulations of internal emitters and external radiation sources. Most of the current studies on AuNP focus on external beam therapy. In contrast, we apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. These results are the foundation for future experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au.
Additional description and genome analyses of Caenorhabditis auriculariae representing the basal lineage of genus Caenorhabditis
Authors: Dayi Mehmet , Kanzaki Natsumi , Sun Simo , Ide Tatsuya , Tanaka Ryusei , Masuya Hayato , Okabe Kimiko , Kajimura Hisashi , Kikuchi Taisei 
Published: March 2021

AbstractCaenorhabditis auriculariae,which was morphologically described in 1999, was re-isolated from aPlatydemamushroom-associated beetle. Based on the re-isolated materials, some morphological characteristics were re-examined and ascribed to the species. In addition, to clarify phylogenetic relationships with otherCaenorhabditisspecies and biological features of the nematode, the whole genome was sequenced and assembled into 109.5 Mb with 16,279 predicted protein-coding genes. Molecular phylogenetic analyses based on ribosomal RNA and 269 single-copy genes revealed the species is closely related toC. sonoraeandC. monodelphisplacing them at the most basal clade of the genus.C. auriculariaehas morphological characteristics clearly differed from those two species and harbours a number of species-specific gene families, indicating its usefulness as a new outgroup species forCaenorhabditisevolutionary studies. A comparison of carbohydrate-active enzyme (CAZy) repertoires in genomes, which we found useful to speculate about the lifestyle ofCaenorhabditisnematodes, suggested thatC. auriculariaelikely has a life-cycle with tight-association with insects.