Causes and Consequences of Spatial Within-Host Viral Spread

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Recent experimental studies, however, have started to shed more light on the mechanisms and spatial dynamics of viral spread within hosts. Here, we review these experimental studies as well as the limited number of computational modeling efforts that have begun to integrate spatial considerations for understanding within-host viral spread. We limit our review to influenza virus to highlight key mechanisms affecting spatial aspects of viral spread for pathogens of the respiratory tract. There is considerable empirical evidence for highly spatial within-host spread of influenza virus, yet few computational modeling studies that shed light on possible factors that structure the dynamics of this spatial spread. In existing modeling studies, there is also a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature to provide informed theoretical expectations for what viral and host factors may impact the spatial patterns of within-host viral dynamics and for how spatial spread will affect the genetic composition of within-host viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host influenza virus spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

Download Full-text

Causes and Consequences of Spatial Within-Host Viral Spread

Viruses ◽

10.3390/v10110627 ◽

2018 ◽

Vol 10 (11) ◽

pp. 627 ◽

Cited By ~ 21

Author(s):

Molly Gallagher ◽

Christopher Brooke ◽

Ruian Ke ◽

Katia Koelle

Keyword(s):

Influenza A ◽

Current Knowledge ◽

Control Strategies ◽

Experimental Studies ◽

Spatial Dynamics ◽

Spatial Process ◽

Influenza A Viruses ◽

Long Distance ◽

Viral Spread ◽

Shed Light

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Here, with a focus on influenza A viruses (IAVs), we first review experimental studies that have shed light on the mechanisms and spatial dynamics of viral spread within hosts. These studies provide strong empirical evidence for highly localized IAV spread within hosts. Since mathematical and computational within-host models have been increasingly used to gain a quantitative understanding of observed viral dynamic patterns, we then review the (relatively few) computational modeling studies that have shed light on possible factors that structure the dynamics of spatial within-host IAV spread. These factors include the dispersal distance of virions, the localization of the immune response, and heterogeneity in host cell phenotypes across the respiratory tract. While informative, we find in these studies a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature on range expansions to provide informed theoretical expectations. We find that factors such as the type of density dependence, the frequency of long-distance dispersal, specific life history characteristics, and the extent of spatial heterogeneity are critical factors affecting the speed of population spread and the genetic composition of spatially expanding populations. For each factor that we identified in the theoretical literature, we draw parallels to its analog in viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host IAV spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

Download Full-text

Report on the spatial spread of defective interfering particles and its role in suppressing infectious particles

10.1101/558932 ◽

2019 ◽

Cited By ~ 1

Author(s):

Qasim Ali ◽

Ruian Ke

Keyword(s):

Functional Organization ◽

Experimental Studies ◽

Reaction Diffusion ◽

Vital Role ◽

Reaction Diffusion Equations ◽

Wild Type Virus ◽

Spatial Process ◽

Spatial Spread ◽

Defective Interfering Particles ◽

The Impact

AbstractDefective interfering particles (DIPs) are categorized as non-infectious viruses with large deletions in their genomic material. A cell infected by a DIP require co-infection by a wild-type virus to complete its replicative lifecycle. There is an increasing interest in developing DIP based therapies in the form of molecular parasites that steal genetic resources of infectious particles. This parasitic behavior is enhanced by constructing engineering designs of DIPs to optimize their role in suppressing the virus infection within-host. Recent experimental studies characterize viral infection as a spatial process and emphasize on its spread rate and the area populated by the infectious particles (IPs). We developed a spatio-temporal model in the framework of reaction-diffusion equations to depict the functional organization of virus particles distributed over a tissue surface. Our model investigates the scenarios and figures out the aspects that can play a vital role to suppress the infection within-host. We studied the impact of initial dose of DIPs, the efficiency of DIP production and the role of cell maturation. Our results show that an engineered DIP can substantially decrease the concentration of IPs. We assert that the decrease in the rate of spatial spread of IPs requires non-deterministic settings.

Download Full-text

Amruthapala (Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter): A Comprehensive Review on Diversity, Therapeutic Uses, and Valorization of Bioactive Constituents

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190318115504 ◽

2019 ◽

Vol 20 (5) ◽

pp. 376-389 ◽

Cited By ~ 1

Author(s):

Sonali Mishra ◽

Nupur Srivastava ◽

Velusamy Sundaresan ◽

Karuna Shanker

Keyword(s):

Secondary Metabolite ◽

Current Knowledge ◽

Experimental Studies ◽

Critical Discussion ◽

Future Research ◽

Bioactive Constituents ◽

Medicinal Uses ◽

Comprehensive Review ◽

Therapeutic Uses ◽

Decalepis Arayalpathra

Background: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. Objective: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. Materials and Methods: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of ‘Ayurveda’ and ‘Siddha’ published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. Results: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the ‘critically endangered’ category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. ‘Amruthapala’ offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. Results: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), β-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).

Download Full-text

Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽

10.3390/cells10040723 ◽

2021 ◽

Vol 10 (4) ◽

pp. 723

Author(s):

Hafid Ait-Oufella ◽

Jean-Rémi Lavillegrand ◽

Alain Tedgui

Keyword(s):

T Cell ◽

Current Knowledge ◽

Experimental Studies ◽

Therapeutic Approaches ◽

Coronary Patients ◽

Cell Subpopulations ◽

Atherosclerotic Process ◽

T Cell Subpopulations ◽

Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

Download Full-text

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽

10.3390/molecules26092506 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2506

Author(s):

Wamidh H. Talib ◽

Ahmad Riyad Alsayed ◽

Alaa Abuawad ◽

Safa Daoud ◽

Asma Ismail Mahmod

Keyword(s):

Clinical Trials ◽

Current Knowledge ◽

Biological Activities ◽

Experimental Studies ◽

Therapeutic Effects ◽

Cell Proliferation Inhibition ◽

Different Types ◽

Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

Download Full-text

Controlling the Spatial Spread of a Xylella Epidemic

Bulletin of Mathematical Biology ◽

10.1007/s11538-021-00861-z ◽

2021 ◽

Vol 83 (4) ◽

Author(s):

Sebastian Aniţa ◽

Vincenzo Capasso ◽

Simone Scacchi

Keyword(s):

Spatial Structure ◽

Numerical Simulations ◽

Control Strategies ◽

Xylella Fastidiosa ◽

Cost Effective ◽

Olive Tree ◽

Control Measures ◽

Weed Biomass ◽

Spatial Spread ◽

Olive Trees

AbstractIn a recent paper by one of the authors and collaborators, motivated by the Olive Quick Decline Syndrome (OQDS) outbreak, which has been ongoing in Southern Italy since 2013, a simple epidemiological model describing this epidemic was presented. Beside the bacterium Xylella fastidiosa, the main players considered in the model are its insect vectors, Philaenus spumarius, and the host plants (olive trees and weeds) of the insects and of the bacterium. The model was based on a system of ordinary differential equations, the analysis of which provided interesting results about possible equilibria of the epidemic system and guidelines for its numerical simulations. Although the model presented there was mathematically rather simplified, its analysis has highlighted threshold parameters that could be the target of control strategies within an integrated pest management framework, not requiring the removal of the productive resource represented by the olive trees. Indeed, numerical simulations support the outcomes of the mathematical analysis, according to which the removal of a suitable amount of weed biomass (reservoir of Xylella fastidiosa) from olive orchards and surrounding areas resulted in the most efficient strategy to control the spread of the OQDS. In addition, as expected, the adoption of more resistant olive tree cultivars has been shown to be a good strategy, though less cost-effective, in controlling the pathogen. In this paper for a more realistic description and a clearer interpretation of the proposed control measures, a spatial structure of the epidemic system has been included, but, in order to keep mathematical technicalities to a minimum, only two players have been described in a dynamical way, trees and insects, while the weed biomass is taken to be a given quantity. The control measures have been introduced only on a subregion of the whole habitat, in order to contain costs of intervention. We show that such a practice can lead to the eradication of an epidemic outbreak. Numerical simulations confirm both the results of the previous paper and the theoretical results of the model with a spatial structure, though subject to regional control only.

Download Full-text

The Neuroinflammatory Role of Pericytes in Epilepsy

Biomedicines ◽

10.3390/biomedicines9070759 ◽

2021 ◽

Vol 9 (7) ◽

pp. 759

Author(s):

Gaku Yamanaka ◽

Fuyuko Takata ◽

Yasufumi Kataoka ◽

Kanako Kanou ◽

Shinichiro Morichi ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Current Knowledge ◽

Morphological Changes ◽

Cell Damage ◽

Neurovascular Unit ◽

Experimental Studies ◽

Intractable Epilepsy ◽

In Vivo Studies

Pericytes are a component of the blood–brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1β, TNFα, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1β, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders.

Download Full-text

The Antiviral Properties of Cyclosporine. Focus on Coronavirus, Hepatitis C Virus, Influenza Virus, and Human Immunodeficiency Virus Infections

Biology ◽

10.3390/biology9080192 ◽

2020 ◽

Vol 9 (8) ◽

pp. 192 ◽

Cited By ~ 3

Author(s):

Paulina Glowacka ◽

Lidia Rudnicka ◽

Olga Warszawik-Hendzel ◽

Mariusz Sikora ◽

Mohamad Goldust ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Influenza Virus ◽

Hepatitis C ◽

Beneficial Effect ◽

Bacterial Infections ◽

Viral Infections ◽

Skin Diseases ◽

Current Knowledge ◽

Immunosuppressive Treatment ◽

Immunodeficiency Virus

This review updates current knowledge regarding the risk of viral infections, including COVID-19, in patients treated with cyclosporine. We also shortly refer to bacterial infections and parasitic infestations in patients treated with cyclosporin. Cyclosporine is an immunosuppressive drug, which is widely used in medicine, including in the treatment of autoimmune skin diseases in dermatology, rheumatology, ophthalmology and nephrology, and in organ transplantation. A usual concern associated with immunosuppressive treatment is the potential risk of infections. Interestingly, several data indicate a relatively low risk of infections, especially viral infections, in patients receiving cyclosporine. It was shown that cyclosporine exerts an inhibitory effect on the replication of some viruses, or may have a potentially beneficial effect on the disease course in infections. These include hepatitis C, influenza virus, rotavirus, human immunodeficiency virus and coronavirus infections. Available data indicate that cyclosporine may have a beneficial effect on COVID-19, which is caused by the coronavirus SARS-COV2.

Download Full-text

Sampled-data extended state observer-based backstepping control of two-link flexible manipulator

Transactions of the Institute of Measurement and Control ◽

10.1177/0142331219832954 ◽

2019 ◽

Vol 41 (13) ◽

pp. 3581-3599 ◽

Cited By ~ 3

Author(s):

Umesh Kumar Sahu ◽

Bidyadhar Subudhi ◽

Dipti Patra

Keyword(s):

Control Strategies ◽

Estimation Error ◽

Experimental Studies ◽

State Observer ◽

Lyapunov Theory ◽

Extended State Observer ◽

Flexible Manipulator ◽

Sampled Data ◽

Extended State ◽

Model Uncertainties

Currently, space robots such as planetary robots and flexible-link manipulators (FLMs) are finding specific applications to reduce the cost of launching. However, the structural flexible nature of their arms and joints leads to errors in tip positioning owing to tip deflection. The internal model uncertainties and disturbance are the key challenges in the development of control strategies for tip-tracking of FLMs. To deal with these challenges, we design a tip-tracking controller for a two-link flexible manipulator (TLFM) by developing a sampled-data extended state observer (SD-ESO). It is designed to reconstruct uncertain parameters for accurate tip-tracking control of a TLFM. Finally, a backstepping (BS) controller is designed to attenuate the estimation error and other bounded disturbances. Convergence and stability of the proposed control system are investigated by using Lyapunov theory. The benefits (control performance and robustness) of the proposed SD-ESO-based BS controller are compared with other similar approaches by pursuing both simulation and experimental studies. It is observed from the results obtained that SD-ESO-based BS Controller effectively compensates the deviation in tip-tracking performance of TLFM due to non-minimum phase behavior and model uncertainties with an improved transient response.

Download Full-text