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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
All organisms are assailed by parasites, and the need for immunity is not restricted to vertebrates. Accordingly, to provide some evolutionary perspective on immunity, we first briefly highlight a few of the remarkable defense capacities of prokaryotes in their ongoing battles with viruses. We do this in part because one of the ways prokaryotes cope with viruses has been co-opted by us as a major gene-editing tool called CRISPR (clustered regularly interspaced short palindromic repeats). We next discuss some of the immune responses of plants, which must also contend with a broad range of parasites. We then examine immunity in invertebrate animals and proceed to vertebrate host defense and the special problems posed by eukaryotic parasites. We conclude the chapter by scrutinizing the insidious ploys that parasites use to evade or manipulate host defenses. As we contemplate this broad palette of biological interactions and seek general principles, we must also realize that even within particular host lineages, there is no one stereotypic solution to achieving protection from parasite attack. Parasites with different evolutionary histories and with highly variable life cycles have selected for marvelously diverse defense systems, the ongoing study of which continues to reveal unforeseen complexities and surprises.
Background and content
Published in Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang, Chinese and Botanical Medicines, 2017
Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang
Despite the worldwide efforts in the past century, the scientific inquiry of botanicals remains a very challenging task. Botanicals usually contain complex chemical mixtures and their interaction in the human body may be much more complicated to follow than a single entity drug. Although outside the scope of this book, it should be recognized that the reductionist approach—to isolate compounds and evaluate their individual activities—has not been sufficient to fully elucidate the biological interactions of the botanicals in the body. The recent advances in systems biology, metabolomics, and chemometrics offer new technological platforms to study complex mixtures and to evaluate corresponding biological responses more effectively. These approaches are holistic, more integrated, and may provide a new tool to advance our understanding of the complex actions of botanicals and natural products in our body at an unprecedented level.
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
All organisms are assailed by parasites, and the need for immunity is not restricted to vertebrates. Accordingly, to provide some evolutionary perspective on immunity, we first briefly highlight a few of the remarkable defense capacities of prokaryotes in their ongoing battles with viruses. We next discuss some of the immune responses of plants, which must also contend with a broad a range of parasites. We then examine immunity in invertebrate animals and proceed to vertebrate host defense and the special problems posed by eukaryotic parasites. We conclude the chapter by scrutinizing the insidious ploys that parasites use to evade or manipulate host defenses. As we contemplate this broad palette of biological interactions and seek general principles, we must also realize that even within particular host lineages, there is no one stereotypic solution to achieving protection from parasite attack. Parasites with different evolutionary histories and with highly variable life cycles have selected for marvelously diverse defense systems, the ongoing study of which continues to reveal unforeseen complexities and surprises.
What is the current value of fluorescence polarization assays in small molecule screening?
Published in Expert Opinion on Drug Discovery, 2020
FP-based assays will continue to be in the forefront of biochemical HTS technologies. Biological interactions are better described when the interacting partners are considered to be in their ‘natural’ milieu. Thus, FP has the advantage of resisting some significant in situ optical interferences [2,p.813,4]. Although the development of suitable fluorescent tracers may be complicated in special cases, their use pays off quickly because of the simplicity and reliability of FP-based binding assays. Furthermore, malfunctioning of the G-protein-coupled galanin receptor type 2, melanocortin 1 receptor, and formyl peptide receptor 2 is correlated with epilepsy, obesity, and Alzheimer’s disease, respectively. Many enzymes and G-protein-coupled receptors (GPCRs) are associated with severe diseases and therefore necessitate new and improved drugs. Thus, improved screening assays are an important component of the discovery of novel compounds. Alternatively, SPR has been used to screen 6,369 compounds as potential GPCR ligands (neurotensin receptor 1) [8].
A Bayesian semiparametric approach to learning about gene–gene interactions in case-control studies
Published in Journal of Applied Statistics, 2018
Durba Bhattacharya, Sourabh Bhattacharya
One of the main challenges faced at the very onset of investigating genetic interactions is that of non-uniqueness in the definition of epistasis or gene–gene interactions. According to Phillips [23], biologically, epistasis can be categorized as functional epistasis and compositional epistasis, both of which differ widely from the statistical definition of epistasis. While functional epistasis indicates protein-protein interactions at molecular level, any disruption of which is explained by a genetic consequence, compositional epistasis refers to blocking of one allelic effect by an allele at another locus. Fisher [10] (see also [13]) defined statistical interaction among the genes as deviations from additive marginal effects of individual genes. Although VanderWeele [29] derived some strong empirical conditions under which statistical interactions correspond to compositional epistasis, a prevailing opinion reflected in both genetic and epidemiological literature suggests limitations of the tests based on Fisher's statistical definition of epistasis in explaining the gene–gene interactions in the biological sense of the term. According to Cordell [7] and Wang et al. [31], although statistical and biological interpretations of interaction need not be compatible with each other, quantification of biological interaction should be based on statistical concepts of interactions.
Application of Bayesian networks in determining nanoparticle-induced cellular outcomes using transcriptomics
Published in Nanotoxicology, 2019
Irini Furxhi, Finbarr Murphy, Craig A. Poland, Barry Sheehan, Martin Mullins, Paride Mantecca
The term nanoparticles (NPs) covers particulates with one or more dimensions in the sub-100 nm size range which can differ widely in composition, size, shape and solubility as well as other physicochemical properties. They are not a single entity and the diversity in properties is only matched by the range of possible biological interactions associated with such NP properties. This creates a significant challenge for pro-active risk characterization for the adequate prevention of human and/or environmental health effects whilst still reaping the societal benefits of nanotechnology. This is further compounded by the rate of development in nanotechnologies and their increasingly widespread use in commercial products such as electronic devices, food packaging and health care.