Swimming Escherichia coli Cells Explore the Environment by Lévy Walk.

Escherichia coli cells swim in aqueous environment in a random walk of alternating runs and tumbles. The diffusion characteristics of this random walk remains unclear. In this study, by tracking the swimming of wild-type cells in a three-dimensional (3D) homogeneous environment, we found that their trajectories are superdiffusive, consistent with Lévy walk behavior. For comparison, we tracked the swimming of mutant cells that lack the chemotaxis signaling noise (the steady-state fluctuation of the concentration of the chemotaxis response regulator CheY-P) and found that their trajectories are normal diffusive. Therefore, wild-type E. coli cells explore the environment by Lévy walk, which originates from the chemotaxis signaling noise. This Lévy walk pattern enhances their efficiency in environmental exploration.IMPORTANCEE. coli cells explore the environment in a random walk of alternating runs and tumbles. By tracking the 3D trajectories of E. coli cells in an aqueous environment, we found that their trajectories are superdiffusive, with a power-law shape for the distribution of run lengths, which is characteristics of Lévy walk. We further show that this Lévy walk behavior is due to the random fluctuation of the output level of the bacterial chemotaxis pathway, and it enhances the efficiency of the bacteria in exploring the environment.

NLRP3 inflammasome mediates angiotensin II-induced islet ß cell apoptosis.

Elevation of angiotensin II (Ang II) in the serum of patients with diabetes is known to promote apoptosis of islet ß cells, but the underlying mechanism remains unclear. The aim of the present study was to explore the role of Nod-like receptor protein 3 (NLRP3) inflammasome in Ang II-induced apoptosis of pancreatic islet ß cells and investigate the possible underlying mechanism. The effect of Ang II on INS-1 cell (a rat insulinoma cell line) viability was detected by CCK-8 method. The cell apoptosis was detected by flow cytometry and western blot analysis. The effect of Ang II on the expressions of thioredoxin-interacting protein (TXNIP) and NLRP3 protein was detected by western blot analysis. The expression of TXNIP mRNA was detected by real-time polymerase chain reaction. The results showed that Ang II was able to reduce INS-1 cell viability and promote apoptosis and at the same time up-regulate the expressions of TXNIP and NLRP3 components. Ang II-induced apoptosis was inhibited after administration of the NLRP3 inhibitor MCC950, and TXNIP silencing could reduce the NLRP3 expression and apoptosis, while both effects of Ang II on TXNIP-NLRP3 and its apoptosis-inducing effect were inhibited by angiotensin II type I receptor (AT1R) blocker Telmisartan. Our results demonstrated that the TXNIP-NLRP3 inflammasome pathway mediated Ang II-induced INS-1 cell apoptosis and might hopefully become a novel target for the treatment of diabetes mellitus.

[Angiotensin II promotes the expression of TXNIP through angiotensin II type 1 receptor in islet ß cells].

This study investigated the effect of angiotensin II (Ang II) on apoptosis and thioredoxin-interacting protein (TXNIP) expression in INS-1 islet cells and the underlying mechanism. INS-1 cells cultured in vitro were treated with different concentration of Ang II for different time, and the viability was measured using cell counting kit-8 (CCK-8). After treatment with 1 × 10-6 mol/L Ang II for 24 h, flow cytometry and Western blot were used to measure the cell apoptosis, and Western blot was used to analyze the protein expression of TXNIP, carbohydrate response element-binding protein (ChREBP) and angiotensin II type 1 receptor (AT1R). Real-time PCR was used to detect TXNIP and ChREBP mRNA expression. IF/ICC was used to observe the TXNIP, ChREBP and AT1R expression. The results showed that Ang II reduced cell viability and induced the expression of TXNIP in a dose- and time-dependent manner (P < 0.05, n = 6) compared with the control group. Ang II induced apoptosis and up-regulated the expression of ChREBP and AT1R (P < 0.05, n = 6). AT1R inhibitor, telmisartan (TM), blocked Ang II-induced TXNIP and ChREBP overexpression (P < 0.05, n = 6) and inhibited Ang II-induced apoptosis. Taken together, Ang II increased ChREBP activation through AT1R, which subsequently increased TXNIP expression and promoted cell apoptosis. These findings suggest a therapeutic potential of targeting TXNIP in preventing Ang II-induced INS-1 cell apoptosis in diabetes.

[Adenovirus-mediated overexpression of thioredoxin interaction protein inhibits INS-1 islet ß cell proliferation].

Diabetes can cause a significant increase in the expression of thioredoxin (Trx)-interacting protein (TXNIP), which binds to Trx and inhibits its activity. The present study was aimed to investigate the effect of TXNIP on proliferation of rat INS-1 islet ß cells and the underlying mechanism. TXNIP overexpressing adenovirus vectors (Ad-TXNIP-GFP and Ad-TXNIPc247s-GFP) were constructed and used to infect INS-1 cells. Ad-TXNIPc247s-GFP vector carries a mutant C247S TXNIP gene, and its expression product (TXNIPc247s) cannot attach and inhibit Trx activity. The expression of TXNIP was detected by real-time PCR and Western blot. EdU and Ki67 methods were used to detect cell proliferation. Protein phosphorylation levels of ERK and AKT were detected by Western blot. The results showed that both TXNIP and TXNIPc247s protein overexpressions inhibited the proliferation of INS-1 cells, and the former's inhibitory effect was greater. Moreover, both of the two kinds of overexpressions inhibited the phosphorylation of ERK and AKT. These results suggest that TXNIP overexpression may inhibit the proliferation of INS-1 cells through Trx-dependent and non-Trx-dependent pathways, and the mechanism involves the inhibition of ERK and AKT phosphorylation.

[Effect of diabetic induced thioredoxin interacting protein (TXNIP) on islet cell senescence].

Objective: To investigate whether the increased expression of thioredoxin interacting protein (TXNIP) in diabetes affects the senescence of islet ß cells. Methods: Six normal mice (db/m) and six diabetic mice (db/db) were randomly selected. Fasting blood glucose was measured by blood sugar meter, the expression levels of TXNIP protein, p16, p21 and Rb in pancreatic tissues were detected by Western blot, senescence-associated beta-galactosidase activity in pancreatic tissue was determined by immunochemical staining. INS-1 islet beta cells were randomly divided into 7 groups (n=6), and transfected with lentiviruses (30 µl) for 4 to 6 hours, then was screened with puromycin (PM, 3 µg/m) for 7 days to construct normal group, scramble ShRNA group (interference with airborne poison group), TXNIP-ShRNA-1 group (TXNIP silence group-1), TXNIP-ShRNA-2 group (TXNIP silence group 2), TXNIP-ShRNA-3 group (TXNIP silence group 3), Ad-GFP group (overexpression of the air virus group), Ad-TXNIP-GFP group (TXNIP overexpression group) stably transferred INS-1 islet beta cell line. TXNIP protein expression was detected by Western blot, aging-related beta-galactosidase activity was detected by immunochemical staining, the changes of expression of p16, p21 and Rb was determined by Western blot. Results: Compared with normal mice, the fasting blood glucose of db/db group was increased significantly (P＜0. 01), the expression of TXNIP protein was increased significantly in pancreatic tissues(P＜0. 05), positive staining rate of ß- galactosidase was increased significantly in pancreatic tissues, p16/p21/Rb protein expression levels were increased significantly (P＜0. 05). Compared with Ad-GFP group, the positive staining rate of ß- galactosidase in Ad-TXNIP-GFP group was increased significantly, p16/p21/Rb protein expression levels were increased significantly (P＜0. 01). Compared to the scramble ShRNA group, the positive staining rate of ß- galactosidase in TXNIP-ShRNA group was decreased, p16/p21/Rb protein expression levels were decreased significantly (P＜0. 05). Conclusion: Diabetes can induce islet ß-cell senescence by up-regulating TXNIP expression.

Prediction of presynaptic and postsynaptic neurotoxins by combining various Chou's pseudo components.

Presynaptic and postsynaptic neurotoxins are two groups of neurotoxins. Identification of presynaptic and postsynaptic neurotoxins is an important work for numerous newly found toxins. It is both costly and time consuming to determine these two neurotoxins by experimental methods. As a complement, using computational methods for predicting presynaptic and postsynaptic neurotoxins could provide some useful information in a timely manner. In this study, we described four algorithms for predicting presynaptic and postsynaptic neurotoxins from sequence driven features by using Increment of Diversity (ID), Multinomial Naive Bayes Classifier (MNBC), Random Forest (RF), and K-nearest Neighbours Classifier (IBK). Each protein sequence was encoded by pseudo amino acid (PseAA) compositions and three biological motif features, including MEME, Prosite and InterPro motif features. The Maximum Relevance Minimum Redundancy (MRMR) feature selection method was used to rank the PseAA compositions and the 50 top ranked features were selected to improve the prediction accuracy. The PseAA compositions and three kinds of biological motif features were combined and 12 different parameters that defined as P1-P12 were selected as the input parameters of ID, MNBC, RF, and IBK. The prediction results obtained in this study were significantly better than those of previously developed methods.