Three dimensional spread analysis of a dengue disease model with numerical season control

Author(s):  
Fereshte Gazori ◽  
Mahmoud Hesaaraki
2019 ◽  
Author(s):  
Friederike Ebner ◽  
Katja Balster ◽  
Katharina Janek ◽  
Agathe Niewienda ◽  
Piotr H. Malecki ◽  
...  

AbstractPreviously, we reported significant immunomodulatory effects of the entire excretory-secretory (ES) proteins of the first larval stage (L1) of the gastrointestinal nematodeTrichuris suisin a rodent model of allergic hyperreactivity. In the present study, we aimed to identify the proteins accounting for the modulatory effects of theT. suisL1 ES proteins and thus studied selected components for their immunomodulatory efficacy in an OVA-induced allergic airway disease model. In particular, an enzymatically activeT. suischitinase mediated amelioration of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung. The three-dimensional structure of theT. suischitinase as determined by high-resolution X-ray crystallography revealed significant similarities to mouse acidic mammalian chitinase (AMCase). In addition, the unique ability ofT. suischitinase to form dimers, as well as acidic surface patches within the dimerization region may contribute to the formation of cross-reactive antibodies to the mouse homologs. This hypothesis is supported by the observation thatT. suischitinase treatment induced cross-reactive antibodies to mouse AMCase and chitinase-like protein BRP-39 in the AHR model. In conclusion, a biologically activeT. suischitinase exhibits immunomodulatory properties despite its structural similarity to the mammalian counterpart.Author summaryExperimental immunotherapy via reintroduction of intestinal worms to treat and prevent autoimmune, chronic inflammatory or allergic diseases is being discussed but the underlying mechanisms are still not fully understood. Here, we investigated the immunomodulatory potential of specific proteins of the whipwormTrichuris suisthat are secreted very early during larval development. Using a murine model of allergic lung disease, we show that in particular oneT. suisprotein, functionally characterized as an active chitinase, is reducing the lung inflammation. TheT. suischitinases three-dimensional protein structure revealed remarkable similarities to the hosts’ chitinase, an enzyme known to play a pivotal role in lung allergy. We also show that treatment with the helminth chitinase induced cross-reactive antibody responses against murine chitinase and chitinase-like proteins, both being inflammatory marker and regulators of type 2 immunity. Thus, our study provides a novel mechanism of immunomodulation by helminth components and may contribute to a better understanding of clinical responses of patients receiving helminthic therapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Shu-Min Guo ◽  
Xue-Zhi Li ◽  
Mini Ghosh

A dengue disease epidemic model with nonlinear incidence is formulated and analyzed. The equilibria and threshold of the model are found. The stability of the system is analyzed through a geometric approach to stability. The proposed model also exhibits backward bifurcation under suitable conditions on parameters. Our results imply that a nonlinear incidence produces rich dynamics and they should be studied carefully in order to analyze the spread of disease more accurately. Finally, numerical simulations are presented to illustrate the analytical findings.


Author(s):  
Huan Ma ◽  
Cong Nie ◽  
Ying Chen ◽  
Jinmiao Li ◽  
Yanjie Xie ◽  
...  

Cell cycle deregulation is involved in pathogenesis of many cancers, and often associated with protein kinase aberrations, including the polo-like kinase 1 (PLK1). Wehereby used retinoblastoma, an intraocular malignancy that lacks targeted therapy, as a disease model and set out to reveal targetability of PLK1 with a small molecularinhibitor ON-01910.Na. First, transcriptomic analysis on patient retinoblastoma tissues suggested that cell cycle progression was deregulated and confirmed that PLK1pathway was upregulated. Next, antitumor activity of ON-01910.Na was investigated inboth cellular and animal levels. Cytotoxicity induced by ON-01910.Na was tumor-specific and dose-dependent in retinoblastoma cells, whilst non-tumor cells wereminimally affected. In three-dimensional culture, ON-01910.Na demonstrated efficient drug-penetrability with multilayer cell death. Post-treatment transcriptomic findingsrevealed that cell cycle arrest and MAPK cascade activation were induced following PLK1 inhibition, and eventually result in apoptotic cell death. In Balb/c nude mice, a safe threshold of 0.8 nmol intravitreal dosage of ON-01910.Na was established for intraocular safety, which was demonstrated by structural integrity and functional preservation. Furthermore, intraocular and subcutaneous xenograft were significantlyreduced with ON-01910.Na treatments. For the first time, we demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. Ourstudy is supportive that local treatment of ON-01910.Na may be a novel, effectivemodality benefiting patients with PLK1-aberrant tumors.


Author(s):  
Youngkyu Cho ◽  
Kyuhwan Na ◽  
Yesl Jun ◽  
Jihee Won ◽  
Ji Hun Yang ◽  
...  

Lymphangiogenesis is a stage of new lymphatic vessel formation in development and pathology, such as inflammation and tumor metastasis. Physiologically relevant models of lymphatic vessels have been in demand because studies on lymphatic vessels are required for understanding the mechanism of tumor metastasis. In this study, a new three-dimensional lymphangiogenesis model in a tumor microenvironment is proposed, using a newly designed macrofluidic platform. It is verified that controllable biochemical and biomechanical cues, which contribute to lymphangiogenesis, can be applied in this platform. In particular, this model demonstrates that a reconstituted lymphatic vessel has an in vivo–like lymphatic vessel in both physical and biochemical aspects. Since biomechanical stress with a biochemical factor influences robust directional lymphatic sprouting, whether our model closely approximates in vivo, the initial lymphatics in terms of the morphological and genetic signatures is investigated. Furthermore, attempting an incorporation with a tumor spheroid, this study successfully develops a complex tumor microenvironment model for use in lymphangiogenesis and reveals the microenvironment factors that contribute to tumor metastasis. As a first attempt at a coculture model, this reconstituted model is a novel system with a fully three-dimensional structure and can be a powerful tool for pathological drug screening or disease model.


2021 ◽  
pp. 002215542110253
Author(s):  
Ida Biunno ◽  
Emanuela Paiola ◽  
Pasquale De Blasio

“Multi-Omics” technologies have contributed greatly to the understanding of various diseases by enabling researchers to accurately and rapidly investigate the molecular circuitry that connects cellular systems. The tissue-engineered, three-dimensional (3D), in vitro disease model “organoid” integrates the “omics” results in a model system, elucidating the complex links between genotype and phenotype. These 3D structures have been used to model cancer, infectious disease, toxicity, and neurological disorders. Here, we describe the advantage of using the tissue microarray (TMA) technology to analyze human-induced pluripotent stem cell–derived cerebral organoids. Compared with the conventional processing of individual samples, sectioning and staining of TMA slides are faster and can be automated, decreasing labor and reagent costs. The TMA technology faithfully captures cell morphology variations and detects specific biomarkers. The use of this technology can scale up organoid research results in at least two ways: (1) in the number of specimens that can be analyzed simultaneously and (2) in the number of consecutive sections that can be produced for analysis with different probes and antibodies.


PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0147564 ◽  
Author(s):  
Kathryn S. Stok ◽  
Bryce A. Besler ◽  
Thomas H. Steiner ◽  
Ana V. Villarreal Escudero ◽  
Martin A. Zulliger ◽  
...  

2020 ◽  
Author(s):  
Kang Huang ◽  
Yaning Han ◽  
Ke Chen ◽  
Hongli Pan ◽  
Wenling Yi ◽  
...  

AbstractObjective quantification of animal behavior is crucial to understanding the relationship between brain activity and behavior. For rodents, this has remained a challenge due to the high-dimensionality and large temporal variability of their behavioral features. Inspired by the natural structure of animal behavior, the present study uses a parallel, and multi-stage approach to decompose motion features and generate an objective metric for mapping rodent behavior into the animal feature space. Incorporating a three-dimensional (3D) motion-capture system and unsupervised clustering into this approach, we developed a novel framework that can automatically identify animal behavioral phenotypes from experimental monitoring. We demonstrate the efficacy of our framework by generating an “autistic-like behavior space” that can robustly characterize a transgenic mouse disease model based on motor activity without human supervision. The results suggest that our framework features a broad range of applications, including animal disease model phenotyping and the modeling of relationships between neural circuits and behavior.


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