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Annual Review of Biomedical Engineering Jun 2023The process of aging manifests from a highly interconnected network of biological cascades resulting in the degradation and breakdown of every living organism over time.... (Review)
Review
The process of aging manifests from a highly interconnected network of biological cascades resulting in the degradation and breakdown of every living organism over time. This natural development increases risk for numerous diseases and can be debilitating. Academic and industrial investigators have long sought to impede, or potentially reverse, aging in the hopes of alleviating clinical burden, restoring functionality, and promoting longevity. Despite widespread investigation, identifying impactful therapeutics has been hindered by narrow experimental validation and the lack of rigorous study design. In this review, we explore the current understanding of the biological mechanisms of aging and how this understanding both informs and limits interpreting data from experimental models based on these mechanisms. We also discuss select therapeutic strategies that have yielded promising data in these model systems with potential clinical translation. Lastly, we propose a unifying approach needed to rigorously vet current and future therapeutics and guide evaluation toward efficacious therapies.
Topics: Humans; Aging; Longevity; Models, Biological; Models, Theoretical; Rejuvenation
PubMed: 37289554
DOI: 10.1146/annurev-bioeng-120122-123054 -
Cell Jul 2022For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this has allowed... (Review)
Review
For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this has allowed researchers to understand many human biological processes in great detail, some developmental and disease mechanisms have proven difficult to study due to inherent species differences. The advent of organoid technology more than 10 years ago has established laboratory-grown organ tissues as an additional model system to recapitulate human-specific aspects of biology. The use of human 3D organoids, as well as other advances in single-cell technologies, has revealed unprecedented insights into human biology and disease mechanisms, especially those that distinguish humans from other species. This review highlights novel advances in organoid biology with a focus on how organoid technology has generated a better understanding of human-specific processes in development and disease.
Topics: Animals; Humans; Models, Biological; Organoids
PubMed: 35868278
DOI: 10.1016/j.cell.2022.06.051 -
Bio Systems Sep 2022One of the fundamental problems of contemporary history is to understand the processes governing the rise and fall of polities. The universality of boom-and-bust...
One of the fundamental problems of contemporary history is to understand the processes governing the rise and fall of polities. The universality of boom-and-bust dynamics associated with the life-cycle of polities tempts to treat the problem mathematically and thus brings it to the framework of cliodynamics. Here we introduce a mathematical model of evolving polity under assumption that its evolution is associated with interactions of certain groups of people, forming the polity and differing by their psycho-ethic characteristics. The model is given in terms of ordinary differential equations and the bust dynamics associated with the rise and fall of polities is modelled as an excitation process, which is the non-linear phenomenon, well known in mathematical biology. We consider the deterministic as well as the stochastic version of the model which we fit to the time-scale of civilization's lifespan. We also expand the model to study interaction between two evolving polities. Investigation is performed using analytical methods as well as numerical integration (i.e. MATLAB simulation).
Topics: Computer Simulation; Humans; Models, Biological; Models, Theoretical; Stochastic Processes
PubMed: 35779699
DOI: 10.1016/j.biosystems.2022.104731 -
Ecology Letters Aug 2022Invasibility, the chance of a population to grow from rarity and become established, plays a fundamental role in population genetics, ecology, epidemiology and...
Invasibility, the chance of a population to grow from rarity and become established, plays a fundamental role in population genetics, ecology, epidemiology and evolution. For many decades, the mean growth rate of a species when it is rare has been employed as an invasion criterion. Recent studies show that the mean growth rate fails as a quantitative metric for invasibility, with its magnitude sometimes even increasing while the invasibility decreases. Here we provide two novel formulae, based on the diffusion approximation and a large-deviations (Wentzel-Kramers-Brillouin) approach, for the chance of invasion given the mean growth and its variance. The first formula has the virtue of simplicity, while the second one holds over a wider parameter range. The efficacy of the formulae, including their accompanying data analysis technique, is demonstrated using synthetic time series generated from canonical models and parameterised with empirical data.
Topics: Ecology; Ecosystem; Models, Biological; Population Dynamics
PubMed: 35717561
DOI: 10.1111/ele.14031 -
Acta Biochimica Et Biophysica Sinica Aug 2022A whole-cell model represents certain aspects of the cell structure and/or function. Due to the high complexity of the cell, an integrative modeling approach is often... (Review)
Review
A whole-cell model represents certain aspects of the cell structure and/or function. Due to the high complexity of the cell, an integrative modeling approach is often taken to utilize all available information including experimental data, prior knowledge and prior models. In this review, we summarize an emerging workflow of whole-cell modeling into five steps: (i) gather information; (ii) represent the modeled system into modules; (iii) translate input information into scoring function; (iv) sample the whole-cell model; (v) validate and interpret the model. In particular, we propose the integrative modeling of the cell by combining available (whole-cell) models to maximize the accuracy, precision, and completeness. In addition, we list quantitative predictions of various aspects of cell biology from existing whole-cell models. Moreover, we discuss the remaining challenges and future directions, and highlight the opportunity to establish an integrative spatiotemporal multi-scale whole-cell model based on a community approach.
Topics: Models, Biological
PubMed: 36017893
DOI: 10.3724/abbs.2022115 -
Bulletin of Mathematical Biology Sep 2022In evolutionary studies, it is common to use phylogenetic trees to represent the evolutionary history of a set of species. However, in case the transfer of genes or...
In evolutionary studies, it is common to use phylogenetic trees to represent the evolutionary history of a set of species. However, in case the transfer of genes or other genetic information between the species or their ancestors has occurred in the past, a tree may not provide a complete picture of their history. In such cases, tree-based phylogenetic networks can provide a useful, more refined representation of the species' evolution. Such a network is essentially a phylogenetic tree with some arcs added between the tree's edges so as to represent reticulate events such as gene transfer, hybridization and recombination. Even so, this model does not permit the direct representation of evolutionary scenarios where reticulate events have taken place between different subfamilies or lineages of species. To represent such scenarios, in this paper we introduce the notion of a forest-based network, that is, a collection of leaf-disjoint phylogenetic trees on a set of species with arcs added between the edges of distinct trees within the collection. Forest-based networks include the recently introduced class of overlaid species forests which can be used to model introgression. As we shall see, even though the definition of forest-based networks is closely related to that of tree-based networks, they lead to new mathematical theory which complements that of tree-based networks. As well as studying the relationship of forest-based networks with other classes of phylogenetic networks, such as tree-child networks and universal tree-based networks, we present some characterizations of some special classes of forest-based networks. We expect that our results will be useful for developing new models and algorithms to understand reticulate evolution, such as introgression and gene transfer between species.
Topics: Humans; Forests; Mathematical Concepts; Models, Biological; Models, Genetic; Phylogeny
PubMed: 36107279
DOI: 10.1007/s11538-022-01081-9 -
Lab Animal Jul 2020Zebrafish have a 50-year history as a model organism for studying vertebrate developmental biology and more recently have emerged as a powerful model system for studying... (Review)
Review
Zebrafish have a 50-year history as a model organism for studying vertebrate developmental biology and more recently have emerged as a powerful model system for studying vertebrate microbiome assembly, dynamics and function. In this Review, we discuss the strengths of the zebrafish model for both observational and manipulative microbiome studies, and we highlight some of the important insights gleaned from zebrafish gut microbiome research.
Topics: Animals; Gastrointestinal Microbiome; Microbiota; Models, Biological; Zebrafish
PubMed: 32541907
DOI: 10.1038/s41684-020-0573-6 -
Developmental Cell Jun 2019Self-organization is pervasive in development, from symmetry breaking in the early embryo to tissue patterning and morphogenesis. For a few model systems, the underlying... (Review)
Review
Self-organization is pervasive in development, from symmetry breaking in the early embryo to tissue patterning and morphogenesis. For a few model systems, the underlying molecular and cellular processes are now sufficiently characterized that mathematical models can be confronted with experiments, to explore the dynamics of pattern formation. Here, we review selected systems, ranging from cyanobacteria to mammals, where different forms of cell-cell communication, acting alone or together with positional cues, drive the patterning of cell fates, highlighting the insights that even very simple models can provide as well as the challenges on the path to a predictive understanding of development.
Topics: Animals; Body Patterning; Cell Communication; Cell Differentiation; Mammals; Models, Biological; Morphogenesis
PubMed: 31163171
DOI: 10.1016/j.devcel.2019.05.019 -
Cell Proliferation Sep 2022Planarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong... (Review)
Review
BACKGROUND
Planarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong regeneration ability. Both the complexity of multiple regulatory networks and their coordinate functions contribute to the maintenance of normal cellular homeostasis and the process of regeneration in planarian. The polarity, size, location and number of regeneration tissues are regulated by diverse mechanisms. In this review we summarize the recent advances about the importance genetic and molecular mechanisms for regeneration control on various tissues in planarian.
METHODS
A comprehensive literature search of original articles published in recent years was performed in regards to the molecular mechanism of each cell types during the planarian regeneration, including neoblast, nerve system, eye spot, excretory system and epidermal.
RESULTS
Available molecular mechanisms gave us an overview of regeneration process in every tissue. The sense of injuries and initiation of regeneration is regulated by diverse genes like follistatin and ERK signaling. The Neoblasts differentiate into tissue progenitors under the regulation of genes such as egfr-3. The regeneration polarity is controlled by Wnt pathway, BMP pathway and bioelectric signals. The neoblast within the blastema differentiate into desired cell types and regenerate the missing tissues. Those tissue specific genes regulate the tissue progenitor cells to differentiate into desired cell types to complete the regeneration process.
CONCLUSION
All tissue types in planarian participate in the regeneration process regulated by distinct molecular factors and cellular signaling pathways. The neoblasts play vital roles in tissue regeneration and morphology maintenance. These studies provide new insights into the molecular mechanisms for regulating planarian regeneration.
Topics: Animals; Homeostasis; Models, Biological; Planarians; Signal Transduction; Stem Cells
PubMed: 35811385
DOI: 10.1111/cpr.13276 -
Methods in Cell Biology 2022The study of protein complexes and protein-protein interactions is of great importance due to their fundamental roles in cellular function. Proximity labeling, often...
The study of protein complexes and protein-protein interactions is of great importance due to their fundamental roles in cellular function. Proximity labeling, often coupled with mass spectrometry, has become a powerful and versatile tool for studying protein-protein interactions by enriching and identifying proteins in the vicinity of a specified protein-of-interest. Here, we describe and compare traditional approaches to investigate protein-protein interactions to current day state-of-the-art proximity labeling methods. We focus on the wide array of proximity labeling strategies and underscore studies using diverse model systems to address numerous biological questions. In addition, we highlight current advances in mass spectrometry-based technology that exhibit promise in improving the depth and breadth of the data acquired in proximity labeling experiments. In all, we show the diversity of proximity labeling strategies and emphasize the broad range of applications and biological inquiries that can be addressed using this technology.
Topics: Mass Spectrometry; Models, Biological
PubMed: 35623704
DOI: 10.1016/bs.mcb.2021.12.006