Combinatorial approaches for introducing additional modifications into lantibiotics

Lantibiotics, a kind of antimicrobial proteins, are attracting more and more interest of researchers all over the world due to their unique bacteria-killing mechanisms resulting from their unique structures. Diverse enzymes are required to construct these structures. In our study, the functionality of different enzymes has been studied in detail on designed peptides. For example, one enzyme (GdmD) can remove the side group (carboxyl group) of the C-terminal cysteine of a designed peptide; another enzyme, LtnJ is able to introduce D-alanine on lantibiotics if the flanking residues of the substrate amino acid are carefully designed. Furthermore, one hydroxylase from actinobacteria, CinX, has been proven to hydroxylate the aspartic acid on lantibiotics. The successful applications of these enzymes to introduce unique structures on designed proteins inspire a new way to expand the diversity of lantibiotics. Using the tools studied in this thesis we are looking forward to finding some novel molecules with improved properties such as stability and specificity

Bacteriocins of lactic acid bacteria:extending the family

Lactic acid bacteria (LAB) constitute a heterogeneous group of microorganisms that produce lactic acid as the major product during the fermentation process. LAB are Gram-positive bacteria with great biotechnological potential in the food industry. They can produce bacteriocins, which are proteinaceous antimicrobial molecules with a diverse genetic origin, posttranslationally modified or not, that can help the producer organism to outcompete other bacterial species. In this review, we focus on the various types of bacteriocins that can be found in LAB and the organization and regulation of the gene clusters responsible for their production and biosynthesis, and consider the food applications of the prototype bacteriocins from LAB. Furthermore, we propose a revised classification of bacteriocins that can accommodate the increasing number of classes reported over the last years

Modeling and Identification of Podded Propulsion Unmanned Surface Vehicle and Its Course Control Research

The response model of podded propulsion unmanned surface vehicle (USV) is established and identified; then considering the USV has characteristic of high speed, the course controller with fast convergence speed is proposed. The idea of MMG separate modeling is used to establish three-DOF planar motion model of the podded propulsion USV, and then the model is simplified as a response model. Then based on field experiments, the parameters of the response model are obtained by the method of system identification. Unlike ordinary ships, USV has the advantages of fast speed and small size, so the controller needs fast convergence speed and strong robustness. Based on the theory of multimode control, a fast nonsingular terminal sliding mode (FNTSM) course controller is proposed. In order to reduce the chattering of system, disturbance observer is used to compensate the disturbance to reduce the control gain and RBF neural network is applied to approximate the symbolic function. At the same time, fuzzy algorithm is employed to realize the mode soft switching, which avoids the unnecessary chattering when the mode is switched. Finally the rapidity and robustness of the proposed control approach are demonstrated by simulations and comparison studies

Lantibiotic Reductase LtnJ Substrate Selectivity Assessed with a Collection of Nisin Derivatives as Substrates

Lantibiotics are potent antimicrobial peptides characterized by the presence of dehydrated amino acids, dehydroalanine and dehydrobutyrine, and (methyl)lanthionine rings. In addition to these posttranslational modifications, some lantibiotics exhibit additional modifications that usually confer increased biological activity or stability on the peptide. LtnJ is a reductase responsible for the introduction of d-alanine in the lantibiotic lacticin 3147. The conversion of l-serine into d-alanine requires dehydroalanine as the substrate, which is produced in vivo by the dehydration of serine by a lantibiotic dehydratase, i.e., LanB or LanM. In this work, we probe the substrate specificity of LtnJ using a system that combines the nisin modification machinery (dehydratase, cyclase, and transporter) and the stereospecific reductase LtnJ in Lactococcus lactis. We also describe an improvement in the production yield of this system by inserting a putative attenuator from the nisin biosynthesis gene cluster in front of the ltnJ gene. In order to clarify the sequence selectivity of LtnJ, peptides composed of truncated nisin and different mutated C-terminal tails were designed and coexpressed with LtnJ and the nisin biosynthetic machinery. In these tails, serine was flanked by diverse amino acids to determine the influence of the surrounding residues in the reaction. LtnJ successfully hydrogenated peptides when hydrophobic residues (Leu, Ile, Phe, and Ala) were flanking the intermediate dehydroalanine, while those in which dehydroalanine was flanked by one or two polar residues (Ser, Thr, Glu, Lys, and Asn) or Gly were either less prone to be modified by LtnJ or not modified at all. Moreover, our results showed that dehydrobutyrine cannot serve as a substrate for LtnJ

Better synchronous binarization for machine translation

Binarization of Synchronous Context Free Grammars (SCFG) is essential for achieving polynomial time complexity of decoding for SCFG parsing based machine translation sys-tems. In this paper, we first investigate the excess edge competition issue caused by a left-heavy binary SCFG derived with the method of Zhang et al. (2006). Then we propose a new binarization method to mitigate the problem by exploring other alternative equivalent bi-nary SCFGs. We present an algorithm that ite-ratively improves the resulting binary SCFG, and empirically show that our method can im-prove a string-to-tree statistical machine trans-lations system based on the synchronous bina-rization method in Zhang et al. (2006) on the NIST machine translation evaluation tasks.

Lack of evidence of hepatitis in patients with oral lichen planus in China: a case control study

Background: China has been one of the countries with high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) liver disease. And lichen planus is an extrahepatic manifestation of patients with chronic HCV infection. This case-control study was conducted to investigate the relationship between oral lichen planus (OLP) and HBV/HCV infection in China. Material and Methods: A total of 776 patients, including 150 patients with OLP (Group OLP), 429 inpatients from the Trauma Ward of Oral and Maxillofacial Surgery Department (Group A), 110 patients with other oral mucosal diseases, but without a reported association with HCV infection (Group B) and 87 patients with oral lichenoid lesion (Group OLL), were compared with their seroprevalence of anti-HCV antibody (HCVAb), hepatitis B surface antigen (HBsAg) and the parameters of liver functions. Moreover, the clinical characteristics of OLP were also observed, such as gender, age, chief complaint, course of the disease, clinical type, sites involved and so on. Results: The positive rates of HCVAb and HBsAg in OLP patients were 0.7% and 4%, respectively. Neither HCVAb nor HBsAg was associated with OLP as demonstrated by both the univariate and the multivariate analyses. The clinical features and liver functions of OLP patients with negative or positive HBsAg were nearly the same. Conclusions: Our findings verify that there is no association between OLP and hepatitis and there is no need to run a screening test for HCV or HBV in OLP patients in Chin

Fuzzy-Based Optimal Adaptive Line-of-Sight Path Following for Underactuated Unmanned Surface Vehicle with Uncertainties and Time-Varying Disturbances

This paper investigates the path following control problem for an underactuated unmanned surface vehicle (USV) in the presence of dynamical uncertainties and time-varying external disturbances. Based on fuzzy optimization algorithm, an improved adaptive line-of-sight (ALOS) guidance law is proposed, which is suitable for straight-line and curve paths. On the basis of guidance information provided by LOS, a three-degree-of-freedom (DOF) dynamic model of an underactuated USV has been used to design a practical path following controller. The controller is designed by combining backstepping method, neural shunting model, neural network minimum parameter learning method, and Nussbaum function. Neural shunting model is used to solve the problem of “explosion of complexity,” which is an inherent illness of backstepping algorithm. Meanwhile, a simpler neural network minimum parameter learning method than multilayer neural network is employed to identify the uncertainties and time-varying external disturbances. In particular, Nussbaum function is introduced into the controller design to solve the problem of unknown control gain coefficient. And much effort is made to obtain the stability for the closed-loop control system, using the Lyapunov stability theory. Simulation experiments demonstrate the effectiveness and reliability of the improved LOS guidance algorithm and the path following controller

Multiobjective Memetic Estimation of Distribution Algorithm Based on an Incremental Tournament Local Searcher

A novel hybrid multiobjective algorithm is presented in this paper, which combines a new multiobjective estimation of distribution algorithm, an efficient local searcher and ε-dominance. Besides, two multiobjective problems with variable linkages strictly based on manifold distribution are proposed. The Pareto set to the continuous multiobjective optimization problems, in the decision space, is a piecewise low-dimensional continuous manifold. The regularity by the manifold features just build probability distribution model by globally statistical information from the population, yet, the efficiency of promising individuals is not well exploited, which is not beneficial to search and optimization process. Hereby, an incremental tournament local searcher is designed to exploit local information efficiently and accelerate convergence to the true Pareto-optimal front. Besides, since ε-dominance is a strategy that can make multiobjective algorithm gain well distributed solutions and has low computational complexity, ε-dominance and the incremental tournament local searcher are combined here. The novel memetic multiobjective estimation of distribution algorithm, MMEDA, was proposed accordingly. The algorithm is validated by experiment on twenty-two test problems with and without variable linkages of diverse complexities. Compared with three state-of-the-art multiobjective optimization algorithms, our algorithm achieves comparable results in terms of convergence and diversity metrics

Alkaline stress reduces root waving by regulating PIN7 vacuolar transport

Root development and plasticity are assessed via diverse endogenous and environmental cues, including phytohormones, nutrition, and stress. In this study, we observed that roots in model plant Arabidopsis thaliana exhibited waving and oscillating phenotypes under normal conditions but lost this pattern when subjected to alkaline stress. We later showed that alkaline treatment disturbed the auxin gradient in roots and increased auxin signal in columella cells. We further demonstrated that the auxin efflux transporter PIN-FORMED 7 (PIN7) but not PIN3 was translocated to vacuole lumen under alkaline stress. This process is essential for root response to alkaline stress because the pin7 knockout mutants retained the root waving phenotype. Moreover, we provided evidence that the PIN7 vacuolar transport might not depend on the ARF-GEFs but required the proper function of an ESCRT subunit known as FYVE domain protein required for endosomal sorting 1 (FREE1). Induced silencing of FREE1 disrupted the vacuolar transport of PIN7 and reduced sensitivity to alkaline stress, further highlighting the importance of this cellular process. In conclusion, our work reveals a new role of PIN7 in regulating root morphology under alkaline stress