The cell line ontology-based representation, integration and analysis of cell lines used in China

Abstract Background The Chinese National Infrastructure of Cell Line stores and distributes cell lines for biomedical research in China. This study aims to represent and integrate the information of NICR cell lines into the community-based Cell Line Ontology (CLO). Results We have aligned, represented, and added all identified 2704 cell line cells in NICR to CLO. We also proposed new ontology design patterns to represent the usage of cell line cells as disease models by inducing tumor formation in model organisms, and the relations between cell line cells and their expressed or overexpressed genes or proteins. The resulting CLO-NICR ontology also includes the Chinese representation of the NICR cell line information. CLO-NICR was merged into the general CLO. To serve the cell research community in China, the Chinese version of CLO-NICR was also generated and deposited in the OntoChina ontology repository. The usage of CLO-NICR was demonstrated by DL query and knowledge extraction. Conclusions In summary, all identified cell lines from NICR are represented by the semantics framework of CLO and incorporated into CLO as a most recent update. We also generated a CLO-NICR and its Chinese view (CLO-NICR-Cv). The development of CLO-NICR and CLO-NIC-Cv allows the integration of the cell lines from NICR into the community-based CLO ontology and provides an integrative platform to support different applications of CLO in China.https://deepblue.lib.umich.edu/bitstream/2027.42/148821/1/12859_2019_Article_2724.pd

Recent expansion and adaptive evolution of the carcinoembryonic antigen family in bats of the Yangochiroptera subgroup

Background: Expansions of gene families are predictive for ongoing genetic adaptation to environmental cues. We describe such an expansion of the carcinoembryonic antigen (CEA) gene family in certain bat families. Members of the CEA family in humans and mice are exploited as cellular receptors by a number of pathogens, possibly due to their function in immunity and reproduction. The CEA family is composed of CEA-related cell adhesion molecules (CEACAMs) and secreted pregnancy-specific glycoproteins (PSGs). PSGs are almost exclusively expressed by trophoblast cells at the maternal-fetal interface. The reason why PSGs exist only in a minority of mammals is still unknown. Results: Analysis of the CEA gene family in bats revealed that in certain bat families, belonging to the subgroup Yangochiroptera but not the Yinpterochiroptera subgroup an expansion of the CEA gene family took place, resulting in approximately one hundred CEA family genes in some species of the Vespertilionidae. The majority of these genes encode secreted PSG-like proteins (further referred to as PSG). Remarkably, we found strong evidence that the ligand-binding domain (IgV-like domain) of PSG is under diversifying positive selection indicating that bat PSGs may interact with structurally highly variable ligands. Such ligands might represent bacterial or viral pathogen adhesins. We have identified two distinct clusters of PSGs in three Myotis species. The two PSG cluster differ in the amino acids under positive selection. One cluster was only expanded in members of the Vespertilionidae while the other was found to be expanded in addition in members of the Miniopteridae and Mormoopidae. Thus one round of PSG expansion may have occurred in an ancestry of all three families and a second only in Vespertilionidae. Although maternal ligands of PSGs may exist selective challenges by two distinct pathogens seem to be likely responsible for the expansion of PSGs in Vespertilionidae. Conclusions: The rapid expansion of PSGs in certain bat species together with selection for diversification suggest that bat PSGs could be part of a pathogen defense system by serving as decoy receptors and/or regulators of feto-maternal interactions

Low Concentrations of Caffeine and Its Analogs Extend the Lifespan of Caenorhabditis elegans by Modulating IGF-1-Like Pathway

Caffeine has been reported to delay aging and protect aging-associated disorders in Caenorhabditis elegans. However, the effects of low concentration of caffeine and its analogs on lifespan are currently missing. Herein, we report that at much lower concentrations (as low as 10 μg/ml), caffeine extended the lifespan of C. elegans without affecting food intake and reproduction. The effect of caffeine was dependent on IGF-1-like pathway, although the insulin receptor homolog, daf-2 allele, e1371, was dispensable. Four caffeine analogs, 1-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, and 1,7-dimethylxanthine, also extended lifespan, whereas 3-methylxanthine and 3,7-dimethylxanthine did not exhibit lifespan-extending activity

Performance of Linear and Nonlinear Two-Leaf Light Use Efficiency Models at Different Temporal Scales

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Exploring the mechanism of aloe-emodin in the treatment of liver cancer through network pharmacology and cell experiments

Objective: Aloe-emodin (AE) is an anthraquinone compound extracted from the rhizome of the natural plant rhubarb. Initially, it was shown that AE exerts an anti-inflammatory effect. Further studies revealed its antitumor activity against various types of cancer. However, the mechanisms underlying these properties remain unclear. Based on network pharmacology and molecular docking, this study investigated the molecular mechanism of AE in the treatment of hepatocellular carcinoma (HCC), and evaluated its therapeutic effect through in vitro experiments.Methods: CTD, Pharmmapper, SuperPred and TargetNet were the databases to obtain potential drug-related targets. DisGenet, GeneCards, OMIM and TTD were used to identify potential disease-related targets. Intersection genes for drugs and diseases were obtained through the Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of intersecting genes were conducted by the website of Bioinformatics. Intersection genes were introduced into STRING to construct a protein-protein interaction network, while the Cytoscape3.9.1 software was used to visualize and analyze the core targets. AutoDock4.2.6 was utilized to achieve molecular docking between drug and core targets. In vitro experiments investigated the therapeutic effects and related mechanisms of AE.Results: 63 overlapped genes were obtained and GO analysis generated 3,646 entries by these 63 intersecting genes. KEGG analysis mainly involved apoptosis, proteoglycans in cancer, TNF signaling pathway, TP53 signaling pathway, PI3K-AKT signaling pathway, etc. AKT1, EGFR, ESR1, TP53, and SRC have been identified as core targets because the binding energies of them between aloe-emodin were less than -5 kcal/Mol.The mRNA and protein expression, prognosis, mutation status, and immune infiltration related to core targets were further revealed. The involvement of AKT1 and EGFR, as well as the key target of the PI3K-AKT signaling pathway, indicated the importance of this signaling pathway in the treatment of HCC using AE. The results of the Cell Counting Kit-8 assay and flow analysis demonstrated the therapeutic effect of AE. The downregulation of EGFR, PI3KR1, AKT1, and BCL2 in mRNA expression and PI3KR1, AKT,p-AKT in protein expression confirmed our hypothesis.Conclusion: Based on network pharmacology and molecular docking, our study initially showed that AE exerted a therapeutic effect on HCC by modulating multiple signaling pathways. Various analyses confirmed the antiproliferative activity and pro-apoptotic effect of AE on HCC through the PI3K-AKT signaling pathway. This study revealed the therapeutic mechanism of AE in the treatment of HCC through a novel approach, providing a theoretical basis for the clinical application of AE

Innate Immune Responses of European Bats Against Lyssaviruses

Bats are ancient mammals that evolved more than 50 million years ago. There are 1,240 different species (> 20% of mammalian species) described so far, which represent one of the most abundant, diverse and widely distributed mammalian groups. Bats are the only mammals which actively fly and therefore can migrate to different areas of the world. It has been increasingly recognized that bats are reservoirs for more than 100 virus species, and several are associated with animal and human epidemics. As natural hosts of rabies virus (RABV) and related lyssaviruses, bats have become a focus of research not only in South America and Africa, but also in Europe and North America. Bats are also considered to be unique in their potential to host emerging and re-emerging zoonotic viruses. To evaluate and reduce the potential risk of rabies transmission to humans or carnivore hosts (like fox, raccoon and dog etc.), active and passive surveillance studies of bat have been performed. Using these approaches diverse lyssaviruses have been detected in bats. However, these studies did not explain the rarely discovered epidemics and the underlying resistance or immune mechanisms in bats as natural hosts for lyssaviruses. Probably, bats are more resistant to lyssavirus infections than other animals. This hypothesis is introducing the research questions of the present thesis: (1) How do the innate immune responses protect bats from fatal outcome of lyssavirus infections? Interferon (IFN) responses which can be induced by the recognition of viruses by pattern recognition receptors act as the first line of defense against lyssavirus infections. Therefore, type I and type III IFNs from European bats were cloned and functionally characterized in this thesis (Chapter 2 and 4). (2) How do the lyssaviruses adapt to escape the host defenses by counteracting the IFN-mediated immune responses? And how do the bats control the viral replication via the IFN responses? To explore the complicated interactions and understand how European bats (Eptesicus serotinus, Myotis myotis and Nyctalus noctula) interact with European bat lyssaviruses (EBLV-1 and 2), a natural host related model for investigations of the bat´s immune system and the virus-host interactions has to be established. Since all of 52 identified European bats species are endangered and strictly protected, stable cell lines from different tissues of M. myotis for in vitro studies were developed and used for molecular and functional studies (Chapter 3 and 4). The data obtained from this thesis revealed that: (a) European bat IFNs do have similar but also distinct molecular characteristics compared with other mammalian IFNs (Chapter 2 and 4); (b) Both investigated bat type I IFNs, IFN-Kappa; and IFN-Omega; present potent anti-lyssaviral activities and display a pathogen associated pattern in the tested cell line (Chapter 2); (c) The established immortalized M. myotis cell lines are differently susceptible to lyssaviruses and contain a functional IFN-mediated signaling cascade (Chapter 3); (d) Bat type III IFN-Lambda;s display cell-type specific functions due to the distinct expression of the IFN-Lambda; receptor (Chapter 4); (e) In bat cell lines a possible evasive strategy of lyssavirus is based on the counteraction of IFN production and/or IFN-mediated defensive pathways (Chapter 3); (f) The higher resistance of brain derived cell line MmBr compared to other cell lines to lyssavirus infection indicates the natural ability of bat´s central nervous system to control the growth of neurotropic virus, which might be an essential reason for the nonclinical outcome (Chapter 3). Overall, the present thesis provides first insights into IFN-mediated innate immune responses against RABV and EBLVs infection in their natural reservoir hosts and an useful toolbox for comparative analysis of virus-host interactions.Fledermäuse sind sehr ursprüngliche Säuger, die sich vor ca. 50 Millionen Jahren entwickelten. Mit jetzt 1.240 beschriebenen Arten sind sie eine der artenreichsten und am weitesten verbreiteten Säugetierordnungen überhaupt. Fledermäuse sind die einzigen Säuger, die aktiv fliegen und daher verschiedenste Gebiete der Welt erreichen konnten. Fledermäuse scheinen auch einzigartig als Wirt für verschiedenste Viren zu sein. Bisher sind mehr als 100 verschiedene Viren in Fledermäusen nachgewiesen, von denen einige Epidemien in anderen Säugern einschließlich des Menschen hervorrufen können. Als natürliche Reservoirwirte für Tollwut und verwandte Lyssaviren sind sie seit längerem Gegenstand intensiver Forschungen weltweit. Aktive und passive Überwachungsstudien wurden durchgeführt, um ein mögliches Übertragungsrisiko von Lyssaviren auf Menschen und andere Wirte (Fuchs, Waschbär, Hund etc.) einschätzen und minimieren zu können. Allerdings erklären solche Untersuchungen noch nicht, warum in Fledermäusen selbst kaum Erkrankungen durch solche Viren beobachtet wurden, noch eine zugrunde liegende Resistenz oder Immunität der Fledermäuse als Reservoirwirte. Offensichtlich ist, dass Fledermäuse resistenter gegen Lyssavirusinfektionen als andere Wirte sind. Dieses Phänomen stand im Vordergrund der vorliegenden Arbeit in der folgenden Fragen untersucht werden sollten: (1) Wie schützt das angeborene Immunsystem Fledermäuse vor einer schwerwiegenden Erkrankung nach Infektion mit Lyssaviren? Welchen Anteil hat die Interferonantwort, die nach Erkennung von Viren durch Muster erkennende Rezeptoren als erste Verteidigungslinie gegen Virusinfektionen fungiert, in Fledermäusen? Um diese Fragen untersuchen zu können, wurden Typ I und Typ III Interferone (IFN) von Europäischen Fledermausarten kloniert und funktionell charakterisiert (Kapitel 2 und 4). (2) Wie haben sich Lyssaviren an den Wirt Fledermaus adaptiert, um der antiviralen Immunantwort durch Beeinflussung der IFN kaskade zu entkommen? Wie wird die virale Replikation durch IFN und IFN induzierte Proteine kontrolliert? Um diese komplexen Interaktionen zwischen Wirt und viralen Pathogen zu untersuchen und verstehen zu können, wie das Immunsystem Europäischer Fledermäuse (Eptesicus serotinus, Myotis myotis und Nyctalus noctula) auf eine Infektion mit Fledermauslyssaviren (EBLV-1 und 2) reagiert, sollte ein Wirtsmodell etabliert werden. Da alle 52 europäischen Fledermausarten vom Aussterben bedroht und daher strikt geschützt sind, sollten permanente Zelllinien verschiedener Gewebe von M. myotis etabliert und in vitro Untersuchungen dieser Fragen funktionell analysiert werden (Kapitel 3 und 4). Die gewonnenen Ergebnisse zeigen: (a) Typ I und Typ III IFN von europäischen Fledermäusen haben eine typische Genstruktur, vergleichbar mit Interferonen anderer Säuger, aber auch einige besondere strukturelle Eigenschaften (Kapitel 2 und 4); (b) Beide charakterisierten Typ I IFN, IFN-Kappa; und IFN-Omega; haben unterschiedlich starke antivirale Aktivität gegen Lyssavirusinfektionen in empfänglichen Zelllinien (Kapitel 2); (c) Die etablierten permanenten Zelllinien von M. myotis sind unterschiedlich empfänglich für Lyssaviren und enthalten eine funktionelle IFN-Signalkaskade (Kapitel 3); (d) Typ III IFN-Lambda; von E. serotinus und M. myotis zeigt Zelltyp spezifische Aktivität in Abhängigkeit des Expressionsniveaus von IFN-Lambda;-Rezeptoren (Kapitel 4); (e) Eine mögliche Strategie von Lyssaviren, der angeborenen Immunantwort zu entkommen besteht in der Blockierung der IFN-Induktion und/oder IFN-indizierter Resistenzmechanismen (Kapitel 3); (f) Die höhere Resistenz der Gehirnzelllinie MmBr gegen Lyssavirusinfektion weist auf eine natürliche Fähigkeit des Zentralnervensystems von Fledermäusen hin, die Replikation der neurotropen Lyssaviren besser kontrollieren zu können (Kapitel 3). Die hier vorgelegten Ergebnisse ermöglichen einen ersten Einblick in die angeborene Immunantwort gegen RABV und EBLV Infektion in einem Reservoirwirt und stellen ein in-vitro-Modell für weitere Untersuchungen zu Wirt-Pathogen-Interaktion in Fledermäusen bereit

Oxygen Consumption and Lethal Dissolved Oxygen Level of Hybrids of Siniperca chuatsi♀ × S. scherzeri♂

Oxygen consumption rate (OCR) and lethal dissolved oxygen levels (DO) of the hybrids (225.3 ± 4.6 g) of Siniperca chuatsi ♀ × S. scherzeri ♂, were determined after acclimating the fish to 15, 20, 26 and 30°C for 20 days. The same parameters were measured for hybrids with different body weight (146.8 ± 6.3 g, 234.3 ± 8.4 g, 273.9 ± 3.3 g, 327 ± 5.1 g) at 26 °C. OCR increased significantly (P <0.05) with increasing acclimation temperature between 20-26°C, and decreased with increasing body weight. Final preferred temperature estimated from the Q10 was between 26-30°C. The lethal DO concentration for the hybrids at 30°C was significantly higher (P <0.05) than at other temperatures. OCR over the daily cycle under natural lighting conditions was also determined at 26°C. It showed a circadian rhythm with the lowest point at 0830 and peak rates at 1430. Results show that the hybrid has a higher stress tolerance and higher stocking density than the female parent S. chuatsi and indicate their culture potential in subtropical freshwater regions

Effects of computational domain on numerical simulation of building fires

Computational fluid dynamics (CFD) modeling (or field modeling) is becoming the main method for numerical simulation of building fires. Among many factors that influence the validity and accuracy of CFD simulation results, the computational domain is sometimes overlooked. In this article, the effects of computational domain on simulation results are analyzed. Simulation results from the use of different domains are compared with experimental data reported in the literature. A parametric study is then conducted to reveal a relationship between the effective domain extension and the heat release rate of the enclosure fire. The effect of computational domain extension in relation to vent opening is also investigated. It is found that the selection of computational domain can have a significant effect on the outcome of enclosure fire simulations. Determination of the appropriate computational domain without unduly sacrificing computational efficiency is also discussed