scholarly journals Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1541
Author(s):  
Louisa F. Ludwig-Begall ◽  
Axel Mauroy ◽  
Etienne Thiry
Keyword(s):  
Vaccine Development ◽  
Analytical Techniques ◽  
Model Systems ◽  
Viral Gastroenteritis ◽  
Viral Reservoirs ◽  
Viral Egress ◽  
Trial Testing ◽  
Direct Acting

Human noroviruses are recognised as the major global cause of viral gastroenteritis. Here, we provide an overview of notable advances in norovirus research and provide a short recap of the novel model systems to which much of the recent progress is owed. Significant advances include an updated classification system, the description of alternative virus-like protein morphologies and capsid dynamics, and the further elucidation of the functions and roles of various viral proteins. Important milestones include new insights into cell tropism, host and microbial attachment factors and receptors, interactions with the cellular translational apparatus, and viral egress from cells. Noroviruses have been detected in previously unrecognised hosts and detection itself is facilitated by improved analytical techniques. New potential transmission routes and/or viral reservoirs have been proposed. Recent in vivo and in vitro findings have added to the understanding of host immunity in response to norovirus infection, and vaccine development has progressed to preclinical and even clinical trial testing. Ongoing development of therapeutics includes promising direct-acting small molecules and host-factor drugs.

scholarly journals Current and Future Antiviral Strategies to Tackle Gastrointestinal Viral Infections

2021 ◽  
Vol 9 (8) ◽  
pp. 1599
Author(s):  
Nanci Santos-Ferreira ◽  
Jana Van Dycke ◽  
Johan Neyts ◽  
Joana Rocha-Pereira
Keyword(s):  
Viral Infections ◽  
Current Knowledge ◽  
Model Systems ◽  
Viral Gastroenteritis ◽  
Library Screening ◽  
Natural Sources ◽  
Repurposed Drugs ◽  
Enteric Adenoviruses

Acute gastroenteritis caused by virus has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The main culprits are rotaviruses, noroviruses, sapoviruses, astroviruses, and enteric adenoviruses. Currently, there are no antiviral drugs available for the prevention or treatment of viral gastroenteritis. Here, we describe the antivirals that were identified as having in vitro and/or in vivo activity against these viruses, originating from in silico design or library screening, natural sources or being repurposed drugs. We also highlight recent advances in model systems available for this (hard to cultivate) group of viruses, such as organoid technologies, and that will facilitate antiviral studies as well as fill some of current knowledge gaps that hamper the development of highly efficient therapies against gastroenteric viruses.

scholarly journals Sweet revenge - Streptococcus pyogenes showcases first example of immune evasion through specific IgG glycan hydrolysis

2019 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Immune Evasion ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Model Systems ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Set Up

AbstractStreptococcus pyogenes (Group A streptococcus, GAS) is an important human pathogen responsible for a wide variety of diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase able to specifically cleave the conserved N-glycan on human IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we were able to characterize the effects of EndoS on host IgG glycosylation during the course of natural infections in human patients. We found substantial IgG glycan hydrolysis locally at site of infection as well as systemically in the most severe cases. Using these findings we were able to set up appropriate model systems to demonstrate decreased resistance to phagocytic killing of GAS lacking EndoS in vitro, as well as decreased virulence in a mouse model of invasive infection. This study represents the first described example of specific bacterial IgG glycan hydrolysis during infection and highlights the importance of IgG glycan hydrolysis for streptococcal pathogenesis. We thereby offer new insights into the mechanism of immune evasion employed by this pathogen with clear implications for treatment of severe GAS infections and future efforts at vaccine development.

scholarly journals Simple Equations Pertaining to the Particle Number and Surface Area of Metallic, Polymeric, Lipidic and Vesicular Nanocarriers

2021 ◽  
Vol 89 (2) ◽  
pp. 15
Author(s):  
M. R. Mozafari ◽  
E. Mazaheri ◽  
K. Dormiani
Keyword(s):  
Drug Delivery ◽  
Surface Area ◽  
Particle Number ◽  
Analytical Techniques ◽  
Metallic Particles ◽  
Nutraceutical Compounds ◽  
Mathematical Formulas ◽  
Simple Equations

Introduction: Bioactive encapsulation and drug delivery systems have already found their way to the market as efficient therapeutics to combat infections, viral diseases and different types of cancer. The fields of food fortification, nutraceutical supplementation and cosmeceuticals have also been getting the benefit of encapsulation technologies. Aim: Successful formulation of such therapeutic and nutraceutical compounds requires thorough analysis and assessment of certain characteristics including particle number and surface area without the need to employ sophisticated analytical techniques. Solution: Here we present simple mathematical formulas and equations used in the research and development of drug delivery and controlled release systems employed for bioactive encapsulation and targeting the sites of infection and cancer in vitro and in vivo. Systems covered in this entry include lipidic vesicles, polymeric capsules, metallic particles as well as surfactant- and tocopherol-based micro- and nanocarriers.

In Vitro and In Vivo Model Systems for the Study of Allergic and Inflammatory Disorders in Man

CHEST Journal ◽  
1985 ◽  
Vol 87 (5) ◽  
pp. 162S-164S ◽  
Author(s):  
Stephen P. Peters ◽  
Robert M. Naclerio ◽  
Alkis Togias ◽  
Robert P. Schleimer ◽  
Donald W. MacGlashan ◽  
...  
Keyword(s):  
Model Systems ◽  
In Vivo Model ◽  
Inflammatory Disorders

scholarly journals Effects of Size and Surface Properties of Nanodiamonds on the Immunogenicity of Plant-Based H5 Protein of A/H5N1 Virus in Mice

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1597
Author(s):  
Thuong Thi Ho ◽  
Van Thi Pham ◽  
Tra Thi Nguyen ◽  
Vy Thai Trinh ◽  
Tram Vi ◽  
...  
Keyword(s):  
High Pressure ◽  
Neutralizing Antibodies ◽  
H5n1 Virus ◽  
Vaccine Development ◽  
Particle Characterization ◽  
Innovative Strategy ◽  
Specific Igg ◽  
Positively Charged

Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40–70 nm (ND40) and ~100–250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.

scholarly journals Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 914
Author(s):  
Melanie V. Brady ◽  
Flora M. Vaccarino
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Human Development ◽  
Disease Modeling ◽  
Model Systems ◽  
Advantages And Disadvantages ◽  
Technical Ability ◽  
Cellular Phenotypes

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.

scholarly journals Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 899
Author(s):  
Clara Liu Chung Ming ◽  
Kimberly Sesperez ◽  
Eitan Ben-Sefer ◽  
David Arpon ◽  
Kristine McGrath ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ex Vivo ◽  
Myocardial Damage ◽  
Cardiovascular Disorder ◽  
Model Systems ◽  
Ex Vivo Model ◽  
Disease Manifestation

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

TMOD-02. GENERATION OF A NOVEL MOUSE MODEL FOR BRAIN TUMORS OF THE DNA METHYLATION CLASS “GBM MYCN”

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi215-vi216
Author(s):  
Melanie Schoof ◽  
Carolin Göbel ◽  
Dörthe Holdhof ◽  
Sina Al-Kershi ◽  
Ulrich Schüller
Keyword(s):  
Dna Methylation ◽  
Brain Tumors ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Tumor Development ◽  
Model Systems ◽  
Preclinical Research ◽  
Human Gbm

Abstract DNA methylation based classification of brain tumors has revealed a high heterogeneity between tumors and led to the description of multiple distinct subclasses. The increasing subdivision of tumors can help to understand molecular mechanisms of tumor development and to improve therapy if appropriate model systems for preclinical research are available. Multiple recent publications have described a subgroup of pediatric glioblastoma which is clearly separable from other pediatric and adult glioblastoma in its DNA methylation profile (GBM MYCN). Many cases in this group are driven by MYCN amplifications and harbor TP53 mutations. These tumors almost exclusively occur in children and were further described as highly aggressive with a median overall survival of only 14 months. In order to further investigate the biology and treatment options of these tumors, we generated hGFAP-cre::TP53 Fl/Fl ::lsl-MYCN mice. These mice carry a loss of TP53 and show aberrant MYCN expression in neural precursors of the central nervous system. The animals develop large forebrain tumors within the first 80 days of life with 100 % penetrance. These tumors resemble human GBM MYCN tumors histologically and are sensitive to AURKA and ATR inhibitors in vitro. We believe that further characterization of the model and in vivo treatment studies will pave the way to improve treatment of patients with these highly aggressive tumors.

Abstract 5402: Two Photon Microscopy Measurements Of Sub-epicardial Sarcomere Length In Perfused Rat Hearts

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Patrizia Camelliti ◽  
Gil Bub ◽  
Daniel J Stuckey ◽  
Christian Bollensdorff ◽  
Damian J Tyler ◽  
...  
Keyword(s):  
Sarcomere Length ◽  
Left Ventricular ◽  
Model Systems ◽  
Future Research ◽  
Fundamental Parameter ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Over Time

Sarcomere length (SL) is a fundamental parameter underlying the Frank Starling relation in the heart, as it offers an absolute representation of myocardial stretch. Previous studies addressed the Frank Starling relation by measuring SL in isolated myocytes or muscle strips. Here, we report first data obtained using a novel technique to measure sub-epicardial SL in perfused hearts. Rat hearts were Langendorff perfused (normal Tyrode solution) at a constant pressure of 90mmHg, labeled with the fluorescent membrane marker di-4-ANEPPS, and then arrested with high-K + Tyrode for either 2-photon microscopy (n=4) or MRI (n=4). Image analysis software was developed to extract SL at the cell level from >1,400 2-photon images (Fig 1 ) and correct for cell angle. SL increased by 10±2 % between 30 and 80 min of perfusion (1.98±0.04 to 2.17±0.03 μm; p<0.05; Fig 1 ). Measurements of left ventricular myocardial volume (LVMV) were made in vivo and in perfused hearts using 3D MRI. LVMV increased by 24±7% from in vivo to 30 min of perfusion, and by 11±3 % between 30 and 90 min (539±35; 664±44; 737±49 mm 3 , respectively; p<0.05; Fig 1 ). We show that SL can be measured in isolated perfused hearts. The method allowed monitoring of changes in SL over time, and showed that SL and LVMV increase to a similar extent during 30–80 min perfusion with crystalloid solution, probably due to tissue oedema. This result, together with the increase in LVMV during the first 30 min, highlights the pronounced differences between in vivo , in situ , and in vitro model systems for studies of cardiac physiology and mechanics. Future research will compare changes in SL in healthy hearts and disease models involving contractile dysfunction. Figure 1: Left: 2-photon microscopy image of di-4-ANEPPS labeled myocardium. Right: SL and LVMV changes over time.

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