Gonadotropin-releasing hormone signaling: An information theoretic approach

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Gonadotropin-releasing hormone (GnRH) is a peptide hormone that mediates central control of reproduction, acting via G-protein coupled receptors that are primarily Gq coupled and mediate GnRH effects on the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. A great deal is known about the GnRH receptor signaling network but GnRH is secreted in short pulses and much less is known about how gonadotropes decode this pulsatile signal. Similarly, single cell measures reveal considerable cell-cell heterogeneity in responses to GnRH but the impact of this variability on signaling is largely unknown. Ordinary differential equation-based mathematical models have been used to explore the decoding of pulse dynamics and information theory-derived statistical measures are increasingly used to address the influence of cell-cell variability on the amount of information transferred by signaling pathways. Here, we describe both approaches for GnRH signaling, with emphasis on novel insights gained from the information theoretic approach and on the fundamental question of why GnRH is secreted in pulses.This work was funded Project Grants from MRC (93447) and the BBSRC (J014699). KTA and MV gratefully acknowledge the financial support of the EPSRC via grant EP/N014391/1 and an MRC Biomedical Informatics Fellowship (MR/K021826/1), respectively

Information Transfer via Gonadotropin-Releasing Hormone Receptors to ERK and NFAT: Sensing GnRH and Sensing Dynamics

This is the final version of the article. Available from Oxford University Press via the DOI in this record.Information theoretic approaches can be used to quantify information transfer via cell signaling networks. In this study, we do so for gonadotropin-releasing hormone (GnRH) activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) in large numbers of individual fixed LβT2 and HeLa cells. Information transfer, measured by mutual information between GnRH and ERK or NFAT, was <1 bit (despite 3-bit system inputs). It was increased by sensing both ERK and NFAT, but the increase was <50%. In live cells, information transfer via GnRH receptors to NFAT was also <1 bit and was increased by consideration of response trajectory, but the increase was <10%. GnRH secretion is pulsatile, so we explored information gained by sensing a second pulse, developing a model of GnRH signaling to NFAT with variability introduced by allowing effectors to fluctuate. Simulations revealed that when cell–cell variability reflects rapidly fluctuating effector levels, additional information is gained by sensing two GnRH pulses, but where it is due to slowly fluctuating effectors, responses in one pulse are predictive of those in another, so little information is gained from sensing both. Wet laboratory experiments revealed that the latter scenario holds true for GnRH signaling; within the timescale of our experiments (1 to 2 hours), cell–cell variability in the NFAT pathway remains relatively constant, so trajectories are reproducible from pulse to pulse. Accordingly, joint sensing, sensing of response trajectories, and sensing of repeated pulses can all increase information transfer via GnRH receptors, but in each case the increase is small.This work was supported by Biochemical and Biophysical Science Research Council Grant BBSRC BB/J014699/1 (to C.A.M. and K.T.-A.). M.V. acknowledges the support of the Medical Research Council (a strategic skills development fellowship in biomedical informatics) and the Engineering and Physical Sciences Research Council via Grant EP/N014391/1

Investigating the Role of Acacia Nilotica Nanoparticles on Promoting Apoptosis in Human Breast Cancer Cell Line (MDA-MB-231)

MDA-MB-231 is a model of a human breast cancer cell line. It represents a suitable cell line for breast cancer research worldwide, including anti-cancer studies. Natural products are rich in phytochemicals that have anti-cancer, antioxidant and anti-inflammatory effects. The aim of this study was to characterize the Acacia nilotica nanoparticles (AN-NPs) from the extract of Acacia nilotica (AN) using transmission electron microscopy (TEM), zeta sizer, X-ray diffraction (XRD) and Fourier transform infrared (FT-IR). Cytotoxic activity was assessed using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The morphological changes of the cells were examined using an inverted microscope. The results showed that at serial concentrations (5, 10, 20, 50 and 70 µg/ml) of AN extract and AN-NPs, a cytotoxic effect and morphological degeneration and damage of the cells were observed. The effect varied depending on the exposure time and AN extract and/or AN-NP concentration on MDA-MB-231. The results showed cytotoxic effects, morphological degeneration, damage and more efficacy against breast cancer cells. We can conclude that AN extract and AN-NP are an effective choice for the development of pharmacological treatments against cancer

Typification of names in the genus Anaphyllum (Araceae)

The little-known and small genus Anaphyllum (Araceae), represented by only two species endemic to India, namely A. beddomei and A. wightii, has remained without correctly designated types. Their syntypes are recognized and the names are here typified. The correct bibliographic reference to the protologue of A. wightii is provided for the first time

Endothelial progenitor cells and integrins: adhesive needs

In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of this cell population as a relevant clinical agent

ICAR: endoscopic skull‐base surgery

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Mutual information estimation - MATLAB code

The file can be opened using MATLABMATLAB function for the estimation of mutual information form cell signalling dat

Dynamic Modelling and Advanced Process Control of Power Block for a Parabolic Trough Solar Power Plant

A fundamental task in the dynamic simulation of parabolic trough power plants (PTPP) is to understand the behavior of the system physics and control loops in the presence of weather variations. This study provides a detailed description of the advanced controllers used in the power block (PB) of a 50 MWel parabolic trough power plant (PTPP). The PB model is achieved using APROS software based on the actual specifications of the existing power plant. To verify the behaviour of the PB model, a comparison between the simulated results and given real data is documented depending on a previous study, and the results indicate a reasonable degree of correspondence. The purpose of this study is to create reference models for the PB. Thereby, developers and engineers will have a better understanding of the state of the art of advanced control loops in these power plants. Moreover, these types of models can be used to specify the most suitable mode of operation for the power plant. In addition, this study gives an overview of dynamic simulation for the design, optimisation and development of power blocks in parabolic trough power plants