TRANSGENIC PLANTS AS A NOVEL BIOREACTOR TO PRODUCE ANTIDIABETIC PROTEINS FOR THE TREATMENT OF TYPE 2 DIABETES

Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex-4) are small peptides with potent insulin secretory effect which makes them attractive drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the synthesis of these small peptides is difficult due to recombinant protein degradation and instability. Human serum transferrin (hTf) is an iron-transport protein that has great potential as an efficient carrier system for protein-based drugs. The use of hTf as a fusion partner will provide a new strategy to enhance the therapeutic potential of GLP-1 and Ex-4. This project investigates the development of transgenic tobacco plants as bioreactors for generating recombinant fusion proteins, GLP-1 - hTf and Ex-4 - hTf. Here, transgenic tobacco plants have successfully accumulated recombinant fusion proteins. Plant-derived proteins showed stability in simulated gastrointestinal environment and confirmed their ability to stimulate insulin secretion from a pancreatic (l-cell line in vitro. Lastly, hTf-fused proteins were shown to internalize into human intestinal epithelial cells in vitro. Collectively, the results suggest that transgenic plants are an effective expression and delivery system of recombinant anti-diabetic proteins

Coevolutionary dynamics of information spreading and heterophilic link rewiring

In many complex systems, the dynamic processes that take place on a network and the changes in the network topology are intertwined. Here, we propose a model of coevolutionary dynamics of information spreading which is accompanied with link rewiring to facilitate the propagation of information. In our model, nodes possessing information attempt to contact new susceptible nodes through the link rewiring while the information spreads on a network. Using moment-closure and heterogeneous mean-field approximations, we examine both the information spread dynamics and network evolution focusing on epidemic size, epidemic threshold, and degree distributions at the steady state. We found that more frequent heterophilic link rewiring leads to a larger epidemic size but does not alter the epidemic threshold. We also observed that link rewiring results in a broader degree distribution in the steady state. This study provides an insight into the the role of the heterophilic link rewiring in both facilitating information propagation and inducing network heterogeneity.Comment: 6 pages, 4 figure

Critical behaviors of cascading dynamics on multiplex two-dimensional lattices

We study the critical phenomena of viable clusters in multiplex two-dimensional lattices using numerical simulations. We identify viable sites on multiplex lattices using two cascading algorithms: the cascade of activations (CA) and deactivations (CD). We found that the giant viable clusters identified by CA and CD processes exhibit different critical behaviors. Specifically, the critical phenomena of CA processes are consistent with the ordinary bond percolation on a single layer but CD processes exhibit the critical behaviors consistent with mutual percolation on multiplex lattices. In addition, we computed the susceptibility of cascading dynamics by using the concept of ghost field. Our results suggest that the CA and CD processes generate viable clusters in different ways.Comment: 6 pages, 6 figure

Drosophila Porin/VDAC Affects Mitochondrial Morphology

Voltage-dependent anion channel (VDAC) has been suggested to be a mediator of mitochondrial-dependent cell death induced by Ca2+ overload, oxidative stress and Bax-Bid activation. To confirm this hypothesis in vivo, we generated and characterized Drosophila VDAC (porin) mutants and found that Porin is not required for mitochondrial apoptosis, which is consistent with the previous mouse studies. We also reported a novel physiological role of Porin. Loss of porin resulted in locomotive defects and male sterility. Intriguingly, porin mutants exhibited elongated mitochondria in indirect flight muscle, whereas Porin overexpression produced fragmented mitochondria. Through genetic analysis with the components of mitochondrial fission and fusion, we found that the elongated mitochondria phenotype in porin mutants were suppressed by increased mitochondrial fission, but enhanced by increased mitochondrial fusion. Furthermore, increased mitochondrial fission by Drp1 expression suppressed the flight defects in the porin mutants. Collectively, our study showed that loss of Drosophila Porin results in mitochondrial morphological defects and suggested that the defective mitochondrial function by Porin deficiency affects the mitochondrial remodeling process

Polyphenolic compounds, antioxidant and anti-inflammatory effects of <i>Abeliophyllum distichum</i> Nakai extract

The present study was conducted to evaluate the antioxidant and anti-inflammatory activities of crude methanolic extract of Abeliophyllum distichum Nakai, and those of its partitioned fractions, including hexane, ethyl acetate, n-butanol, and aqueous. The antioxidant activities were analyzed by DPPH free radical scavenging and oxygen radical antioxidant capacity assay. Results showed that the BuOH fraction possessed a strong antioxidant activity through a hydrogen atom transfer reaction-based mechanism and a single electron transfer reaction-based mechanism. In lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, the BuOH fraction of A. distichum methanol extract exhibited a strong inhibitory effect on the nitric oxide production and inhibited the expression of pro-inflammatory mediators, including COX-2, TNF-α, and IL-6, through the inhibition of the MEK/ERK signaling pathway. In addition, the BuOH fraction inhibited the LPS-induced ROS level through the NADPH oxidase-independent mechanism. Furthermore, HPLC analysis identified chlorogenic acid, caffeic acid, gentisic acid, rutin, ferulic acid, and quercetin, and suggested that the antioxidant and anti-inflammatory activities of the BuOH fraction should be mediated by the presence of higher amounts of caffeic acid, rutin, and ferulic acid than other fractions. Taken together, these results suggest that A. distichum extract is a source of antioxidant and anti-inflammatory compounds, and could be developed as a potential source for functional food and dietary health supplement

The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development

Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2). H3S28ph and MSK1/2 were enriched at the key endocrine and acinar promoters in E12.5 multipotent pancreatic progenitors. Pharmacological inhibition of MSK1/2 in embryonic pancreatic explants promoted the specification of endocrine fates, including the beta-cell lineage, while depleting acinar fates. Germline knockout of both Msk isoforms caused enhancement of alpha cells and a reduction in acinar differentiation, while monoallelic loss of Msk1 promoted beta cell mass. Our screen of chromatin state dynamics can be applied to other developmental contexts to reveal new pathways and approaches to modulate cell fates

Individual-driven versus interaction-driven burstiness in human dynamics

Funding Information: The authors thank Woo-Sik Son for providing us with the preprocessed data set of the English Wikipedia, and Heetae Kim and Jinhyuk Yun for useful discussion. H.-H.J. was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1A09081919). Publisher Copyright: © 2021 authors. Published by the American Physical Society.The origin of non-Poissonian or bursty temporal patterns observed in various data sets for human social dynamics has been extensively studied, yet its understanding still remains incomplete. Considering the fact that humans are social beings, a fundamental question arises: Is the bursty human dynamics dominated by individual characteristics or by interaction between individuals? In this paper we address this question by analyzing the Wikipedia edit history to see how spontaneous individual editors are in initiating bursty periods of editing, i.e., individual-driven burstiness, and to what extent such editors' behaviors are driven by interaction with other editors in those periods, i.e., interaction-driven burstiness. We quantify the degree of initiative (DoI) of an editor of interest in each Wikipedia article by using the statistics of bursty periods containing the editor's edits. The integrated value of the DoI over all relevant timescales reveals which is dominant between individual-driven and interaction-driven burstiness. We empirically find that this value tends to be larger for weaker temporal correlations in the editor's editing behavior and/or stronger editorial correlations. These empirical findings are successfully confirmed by deriving an analytic form of the DoI from a model capturing the essential features of the edit sequence. Thus our approach provides a deeper insight into the origin and underlying mechanisms of bursts in human social dynamics.Peer reviewe