Mathematical modeling and analysis of cancer treatment with radiation and anti-PD-L1.

In cancer treatment, radiation therapy (RT) induces direct tumor cell death due to DNA damage, but it also enhances the deaths of radiosensitive immune cells and is followed by local relapse and up-regulation of immune checkpoint ligand PD-L1. Since the binding between PD-1 and PD-L1 curtails anti-tumor immunities, combining RT and PD-L1 inhibitor, anti-PD-L1, is a potential method to improve the treatment efficacy by RT. Some experiments support this hypothesis by showing that the combination of ionizing irradiation (IR) and anti-PD-L1 improves tumor reduction comparing to the monotherapy of IR or anti-PD-L1.

IL-27 in combination with anti-PD-1 can be anti-cancer or pro-cancer.

Interleukin-27 (IL-27) is known to play opposing roles in immunology. The present paper considers, specifically, the role IL-27 plays in cancer immunotherapy when combined with immune checkpoint inhibitor anti-PD-1. We first develop a mathematical model for this combination therapy, by a system of Partial Differential Equations, and show agreement with experimental results in mice injected with melanoma cells.

Different mechanisms of CD200-CD200R induce diverse outcomes in cancer treatment.

The CD200 is a cell membrane protein expressed by tumor cells, and its receptor CD200 receptor (CD200R) is expressed by immune cells including macrophages and dendritic cells. The formation of CD200-CD200R inhibits the cellular functions of the targeted immune cells, so CD200 is one type of the immune checkpoint and blockade CD200-CD200R formation is a potential cancer treatment. However, the CD200 blockade has opposite treatment outcomes in different types of cancers.

A simple in-host model for COVID-19 with treatments: model prediction and calibration.

In this paper, we provide a simple ODEs model with a generic nonlinear incidence rate function and incorporate two treatments, blocking the virus binding and inhibiting the virus replication to investigate the impact of calibration on model predictions for the SARS-CoV-2 infection dynamics. We derive conditions of the infection eradication for the long-term dynamics using the basic reproduction number, and complement the characterization of the dynamics at short-time using the resilience and reactivity of the virus-free equilibrium are considered to inform on the average time of recovery and sensitivity to perturbations in the initial virus free stage. Then, we calibrate the treatment model to clinical datasets for viral load in mild and severe cases and immune cells in severe cases.

G protein controls stress readiness by modulating transcriptional and metabolic homeostasis in Arabidopsis thaliana and Marchantia polymorpha.

The core G protein signaling module, which consists of Gα and extra-large Gα (XLG) subunits coupled with the Gβγ dimer, is a master regulator of various stress responses. In this study, we compared the basal and salt stress-induced transcriptomic, metabolomic and phenotypic profiles in Gα, Gβ, and XLG-null mutants of two plant species, Arabidopsis thaliana and Marchantia polymorpha, and showed that G protein mediates the shift of transcriptional and metabolic homeostasis to stress readiness status. We demonstrated that such stress readiness serves as an intrinsic protection mechanism against further stressors through enhancing the phenylpropanoid pathway and abscisic acid responses.

Mathematical modeling for the combination treatment of IFN-γ and anti-PD-1 in cancer immunotherapy.

When the immune-checkpoint programmed death-1 (PD-1) binds to its ligand programmed death ligand 1 (PD-L1) to form the complex PD-1-PD-L1, this complex inactivates immune cells resulting in cell apoptosis, downregulation of immune reaction, and tumor evasion. The antibody, anti-PD-1 or anti-PD-L1, blocks the PD-1-PD-L1 complex formation to restore the functions of T cells. Combination of anti-PD-1 with other treatment shows promising in different types of cancer treatments.

Mathematical Modeling and Analysis of CD200-CD200R in Cancer Treatment.

CD200 is a cell membrane protein that binds to its receptor, CD200 receptor (CD200R). The CD200 positive tumor cells inhibit the cellular functions of M1 and M2 macrophages and dendritic cells (DCs) through the CD200-CD200R complex, resulting in downregulation of Interleukin-10 and Interleukin-12 productions and affecting the activation of cytotoxic T lymphocytes. In this work, we provide two ordinary differential equation models, one complete model and one simplified model, to investigate how the binding affinities of CD200R and the populations of M1 and M2 macrophages affect the functions of the CD200-CD200R complex in tumor growth.

Mathematical modeling of the eyespots in butterfly wings.

Butterfly wing color patterns are a representative model system for studying biological pattern formation, due to their two-dimensional simple structural and high inter- and intra-specific variabilities. Moreover, butterfly color patterns have demonstrated roles in mate choice, thermoregulation, and predator avoidance via disruptive coloration, attack deflection, aposematism, mimicry, and masquerade. Because of the importance of color patterns to many aspects of butterfly biology and their apparent tractability for study, color patterns have been the subjects of many attempts to model their development.

Mathematical modeling and analysis of the heat shock protein response during thermal stress in fish and HeLa cells.

The climate change has the potential to dramatically affect species' thermal physiology and may change the ecology and evolution of species' lineages. In this work, we investigated the transition of dynamics in the heat shock response when the thermal stress approaches the upper thermal limits of species to understand how the climate change may affect the heat shock responses in ectotherms and endotherms. The heat shock protein 70, HSP70, prevents protein denaturation or misfolding under thermal stresses.

Long-distance communication in Arabidopsis involving a self-activating G protein.

In plant cells, heterotrimeric G protein signaling mediates development, biotic/abiotic stress responsiveness, hormone signaling, and extracellular sugar sensing. The amount of sugar in plant cells fluctuates from nanomolar to high millimolar concentrations over time depending on changes in the light environment. Regulator of G Signaling protein 1 (AtRGS1) modulates G protein activation and detects the concentration and the exposure time of sugars.

Dose-Duration Reciprocity for G protein activation: Modulation of kinase to substrate ratio alters cell signaling.

In animal cells, activation of heterotrimeric G protein signaling generally occurs when the system's cognate signal exceeds a threshold, whereas in plant cells, both the amount and the exposure time of at least one signal, D-glucose, are used toward activation. This unusual signaling property called Dose-Duration Reciprocity, first elucidated in the genetic model Arabidopsis thaliana, is achieved by a complex that is comprised of a 7-transmembrane REGULATOR OF G SIGNALING (RGS) protein (AtRGS1), a Gα subunit that binds and hydrolyzes nucleotide, a Gβγ dimer, and three WITH NO LYSINE (WNK) kinases. D-glucose is one of several signals such as salt and pathogen-derived molecular patterns that operates through this protein complex to activate G protein signaling by WNK kinase transphosphorylation of AtRGS1.

The kinetics in mathematical models on segmentation clock genes in zebrafish.

Somitogenesis is the process for the development of somites in vertebrate embryos. This process is timely regulated by synchronous oscillatory expression of the segmentation clock genes. Mathematical models expressed by delay equations or ODEs have been proposed to depict the kinetics of these genes in interacting cells.

A nondestructive method to estimate the chlorophyll content of seedlings.

Background: Chlorophyll content decreases in plants under stress conditions, therefore it is used commonly as an indicator of plant health. offers a convenient and fast way to test physiological phenotypes of mutations and treatments. However, chlorophyll measurements with conventional solvent extraction are not applicable to leaves due to their small size, especially when grown on culture dishes.

A shadow detector for photosynthesis efficiency.

Plants tolerate large variations in the intensity of the light environment by controlling the efficiency of solar to chemical energy conversion. To do this, plants have a mechanism to detect the intensity, duration, and change in light as they experience moving shadows, flickering light, and cloud cover. Sugars are the primary products of CO fixation, a metabolic pathway that is rate limited by this solar energy conversion.

The role of the cytokines IL-27 and IL-35 in cancer.

The cancer-immune interaction is a fast growing field of research in biology, where the goal is to harness the immune system to fight cancer more effectively. In the present paper we review recent work of the interaction between T cells and cancer. CD8+ T cells are activated by IL-27 cytokine and they kill tumor cells.

Mathematical modeling of Interleukin-35 promoting tumor growth and angiogenesis.

Interleukin-35 (IL-35), a cytokine from the Interleukin-12 cytokine family, has been considered as an anti-inflammatory cytokine which promotes tumor progression and tumor immune evasion. It has also been demonstrated that IL-35 is secreted by regulatory T cells. Recent mouse experiments have shown that IL-35 produced by cancer cells promotes tumor growth via enhancing myeloid cell accumulation and angiogenesis, and reducing the infiltration of activated CD8[Formula: see text] T cells into tumor microenvironment.

Mathematical modeling of interleukin-27 induction of anti-tumor T cells response.

Interleukin-12 is a pro-inflammatory cytokine which promotes Th1 and cytotoxic T lymphocyte activities, such as Interferon-[Formula: see text] secretion. For this reason Interleukin-12 could be a powerful therapeutic agent for cancer treatment. However, Interleukin-12 is also excessively toxic.

The effect of time delay in a two-patch model with random dispersal.

We consider a two-patch model for a single species with dispersal and time delay. For some explicit range of dispersal rates, we show that there exists a critical value τc for the time delay τ such that the unique positive equilibrium of the system is locally asymptotically stable for τ ∈[0,τc) and unstable for τ > τc .

The role of CD200-CD200R in tumor immune evasion.

CD200 is a cell membrane protein that interacts with CD200 receptor (CD200R) of myeloid lineage cells. During tumor initiation and progression, CD200-positive tumor cells can interact with M1 and M2 macrophages through CD200-CD200R-compex, and downregulate IL-10 and IL-12 productions secreted primarily by M2 and M1 macrophages, respectively. In the tumor microenvironment, IL-10 inhibits the activation of cytotoxic T lymphocytes (CTL), while IL-12 enhances CTL activation.