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Clostridioides difficile (C. difficile) is the leading cause of antibiotic-induced bacterial colitis and life-threatening diarrhea worldwide. The commonly existing anionic polysaccharide II (PSII) ...

At present, most Trojan detection methods are based on the features of host and code. Such methods have certain limitations and lag. This paper analyzes the network behavior features and network traffic of several typical Trojans such as Zeus and Weasel, and proposes a Trojan traffic detection algorithm based on machine learning. First, model different machine learning algorithms and use Random Forest algorithm to extract features for Trojan behavior and communication features. Then identify and detect Trojans' traffic. The accuracy is as high as 95.1%. Comparing the detection of different machine learning algorithms, experiments show that our algorithm has higher accuracy, which is helpful and useful for identifying Trojan.

Bacterial pathogen infections are fast-growing public health threats and worldwide problems. Glycoconjugate vaccines are among the most effective means in combating such infections. Recent advances in bacterial protein glycan coupling technology (PGCT) have revolutionized the production of glycoconjugate vaccines and drawn enormous attention from both researchers and pharmaceutical companies. Cloning of bacterial surface polysaccharide gene cluster is a prerequisite for the application of PGCT. In this study, we applied the RecET direct cloning strategy for rapid and efficient cloning of O-antigen polysaccharide gene clusters from Escherichia coli serotypes O25b, O26, and O55 in a high-fidelity manner. Then, these gene clusters were applied in PGCT to produce corresponding glycoconjugates. Subsequent immunological studies verified the abilities of glycoconjugate vaccine candidates O25-maltose-binding protein (MBP), O26-MBP, and O55-MBP to generate serotype-specific antibodies and confer protection against E. coli infections. The combination of RecET direct cloning and PGCT makes the rapid production of glycoconjugate vaccines against fast-expanding bacterial pathogens possible.

Glycoconjugate vaccine is composed of polysaccharides (PSs) covalently linked with carrier protein. Glycosylation site selection, as a significant factor leading to heterogeneities of glycoconjugate structure, draws more and more attentions for its impact on the immunogenicity of glycoconjugate vaccine. To elucidate the relationship between glycosylation connectivity and immunogenicity of glycoconjugate vaccine, in this study, anti-E. coli O157:H7 glycoconjugate O-PS-MBP with defined connectivity, and three selected peptide segments GS1, GS2, GS3 derived from O-PS-MBP was synthesized. Immunogenicity results showed that only peptides adjacent to the glycosylation sites (GS1 and GS2) promoted the generation of PS-specific IgG antibodies and contributed to PS-specific IgG subclass distribution. Furthermore, GS1 and GS2 had significant priming effect for eliciting PS-specific IgG antibodies. These results indicated that different locations of glycosylation sites could lead to diverse presentation of peptides and glycopeptides to APCs and influence the immunogenicity of glycoconjugate vaccine, which extend the current understanding of mechanism for adaptive immune system activation by glycoconjugate vaccine, and have implications for rational glycoconjugate vaccine design.

RecET direct cloning enables obtaining a large DNA region from genome. Here we describe its applications in cloning of polysaccharide gene cluster from gram-negative bacteria. Rapid and exact cloning of polysaccharide gene cluster can be achieved by this method.

RecET direct cloning enables obtaining a large DNA region from genome. Here we describe its applications in cloning of polysaccharide gene cluster from gram-negative bacteria. Rapid and exact cloning of polysaccharide gene cluster can be achieved by this method.

Vaccines based on melanoma-associated antigens (MAGEs) present a promising strategy for tumor immunotherapy, albeit with weak immunogenicity. In this study, the xenoantigen L-rhamnose (Rha) was chemically conjugated with truncated MAGE-A3 (tMAGE-A3) to generate Rha-tMAGE-A3. The product showed good antigenicity with anti-Rha antibodies purified from human serum. FITC-labeled Rha-tMAGE-A3 was detected in THP-1 human macrophage cells via the anti-Rha antibody-dependent antigen uptake process. Furthermore, peripheral blood mononuclear cells (PBMCs) stimulated with Rha-tMAGE-A3 in the presence of anti-Rha antibodies showed better cytotoxicity toward A375 human melanoma cells surfaced by MAGE-A3 antigen compared to PBMCs stimulated with tMAGE-A3. All data reveal that linking of Rha epitopes to MAGE enhances the immunogenicity of MAGE by harnessing the immune effector functions of human naturally existing anti-Rha antibodies. Rha epitopes could become immunogenicity enhancers of tumor associated antigens in the development of tumor immunotherapies.

A large body of evidence indicates that violent offenders have executive functioning deficits. However, previous studies have not considered childhood trauma, which is likely to influence the executive functioning of violent offenders. The aim of the present study was to compare the difference of executive functioning among juvenile violent offenders, with non-violent offenders and normal controls, and then to analyse whether executive functioning was affected independently of childhood trauma. In addition to using a battery of tests assessing executive functioning including the Intra/Extradimensional Shift Test(IED), the Stockings of Cambridge Test (SOC), and the Spatial Working Memory Test (SWM) from the Cambridge Automated Neuropsychological Testing Battery (CANTAB), the short form of the Chinese Revision of the Wechsler Adult Intelligence Scale (WAIS-RC) and Childhood Trauma Questionnaire-28 item Short Form (CTQ) were also used among 107 violent offenders, 107 non-violent offenders and 107 normal controls. Our results showed that both offender groups obtained significantly lower estimated Intelligence Quotient (IQ) scores and experienced more childhood trauma than did normal controls. Violent offenders showed impaired executive functioning on tasks of attention set-shifting, working memory and planning. Finally, spatial working memory (SWM) deficits, particularly SWM strategy scores, may be associated with childhood trauma.

Background In the process of ABO-incompatible (ABOi) organ transplantation, removal of anti-A and/or B antibodies from blood plasma is a promising method to overcome hyperacute rejection and allograft loss caused by the immune response between anti-A and/or B antibodies and the A and/or B antigens in the recipient. Although there are commercial columns to do this work, the application is still limited because of the high production cost. Results In this study, the PglB glycosylation pathway from Campylobacter jejuni was exploited to produce glycoprotein conjugated with Escherichia coli O86:B7 O-antigen, which bears the blood group B antigen epitope to absorb blood group B antibody in blood. The titers of blood group B antibody were reduced to a safe level without changing the clotting function of plasma after glycoprotein absorption of B antibodies in the plasma. Conclusions We developed a feasible strategy for the specific adsorption/removal of blood group antibodies. This method will be useful in ABOi organ transplantation and universal blood transfusion. Electronic supplementary material The online version of this article (doi:10.1186/s12934-016-0538-z) contains supplementary material, which is available to authorized users.

Additional file 1: Table S1. List of constructed plasmids, strains and primers used in the study. Figure S1. MALDI-TOF detection of MBPmut (a) and MBPmut-OPS (b).

The O-antigen of Gram-negative bacterium plays an important role in the signal identification, adhesion, immune evasion and other processes. There are three O-antigen polysaccharides biosynthesis mechanisms according to the type of the flippase that is involved. The Wzy-dependent mechanism is more commonly seen. In Wzy-dependent mechanism, the wzz gene is involved in regulating the length of O-antigen polysaccharide chain which can affect antigenicity of the pathogen and immune response of the host. Based on the crystal structure of Wzz (regulator of the O- antigen polysaccharides length) , different length of O-antigen chain can be obtained through molecular modification of the gene wzz. Conjugating O-antigen or its mutants of a pathogen to a carrier protein could help to develop a vaccine that have both a good target specificity and a strong immunogenicity. Therefore, it is important to understand the function, structure and mechanism of Wzz for the development and production of glycoconjugates vaccine.

Globotriose is involved in numerous pathogenic processes and drug development strategies. Recent studies have demonstrated that globotriosylceramide could be used in colon cancer therapy and as a crucial indicator for susceptibility to HIV-1 infection. Therefore, the cost-effective and facile approaches for large-scale production of globotiose as potential drugs are highly required. Here, a multi-enzyme one-pot system containing a galactokinase (SpGalK, E.C.2.7.1.6), a UDP-glucose pyrophosphorylase (SpGalU, E.C.2.7.7.9), a α-1,4-galactosyltransferase (LgtC, E.C. 2.4.1.44) and a commercial inorganic pyrophosphatase (PPase, EC 3.6.1.1) was designed to achieve globotriose on preparative scales. This method exploits a cheaper initial substrate, galactose, for donor UDP-galactose production. More importantly, the substrate specificity of SpGalK and SpGalU is highly promiscuous and various UDP-galactose derivatives obtained could be used as the donor substrates for LgtC. This pointcut of rapid preparation of globotriose derivatives is proposed for the first time. Finally, three globotriose analogs were achieved by this one-pot multi-enzyme system in our study.