15 research outputs found
Synthesis of Microbial Sialic Acids and Related Chemical Probes for the Study of Campylobacter jejuni Glycobiology
The thesis combines synthetic carbohydrate chemistry (syntheses of microbial sialic acids and biosynthetic precursors with fluorescent labelling) and genetic studies of C. jejuni. The synthetic endeavours cover a wide range of chemical reactions including a range of carbohydrate specific manipulations alongside complex hydroxylation and oxidation studies and mosher ester analysis. The novelty of the thesis comes from the combination of these approaches, and the final application of the chemical tools within the bacterium
Metabolic Labeling of Legionaminic acid in Flagellin Glycosylation of Campylobacter jejuni Identifies Maf4 as a Putative Legionaminyl Transferase
Campylobacter jejuni is the major human food-borne pathogen. Its bipolar flagella are heavily O-glycosylated with microbial sialic acids and essential for its motility and pathogenicity. However, both the glycosylation of flagella and the exact contribution of legionaminic acid (Leg) to flagellar activity is poorly understood. Herein, we report the development of a metabolic labeling method for Leg glycosylation on bacterial flagella with probes based on azide-modified Leg precursors. The hereby azido-Leg labeled flagellin could be detected by Western blot analysis and imaged on intact bacteria. Using the probes on C. jejuni and its isogenic maf4 mutant we also further substantiated the identification of Maf4 as a putative Leg glycosyltransferase. Further evidence was provided by UPLC–MS detection of labeled CMP-Leg and an in silico model of Maf4. This method and the developed probes will facilitate the study of Leg glycosylation and the functional role of this modification in C. jejuni motility and invasiveness
Metabolic Labeling of Legionaminic acid in Flagellin Glycosylation of Campylobacter jejuni Identifies Maf4 as a Putative Legionaminyl Transferase
Campylobacter jejuni is the major human food-borne pathogen. Its bipolar flagella are heavily O-glycosylated with microbial sialic acids and essential for its motility and pathogenicity. However, both the glycosylation of flagella and the exact contribution of legionaminic acid (Leg) to flagellar activity is poorly understood. Herein, we report the development of a metabolic labeling method for Leg glycosylation on bacterial flagella with probes based on azide-modified Leg precursors. The hereby azido-Leg labeled flagellin could be detected by Western blot analysis and imaged on intact bacteria. Using the probes on C. jejuni and its isogenic maf4 mutant we also further substantiated the identification of Maf4 as a putative Leg glycosyltransferase. Further evidence was provided by UPLC–MS detection of labeled CMP-Leg and an in silico model of Maf4. This method and the developed probes will facilitate the study of Leg glycosylation and the functional role of this modification in C. jejuni motility and invasiveness
Research on variable universe fuzzy PID control for semi-active suspension with CDC dampers based on dynamic adjustment functions
Abstract The vehicle suspension system is a complex system with multiple variables, nonlinearity and time-varying characteristics, and the traditional variable universe fuzzy PID control algorithm has the problems of over-reliance on expert experience and non-adaptive adjustment of the contracting-expanding factor parameters, which make it difficult to achieve a better control effect. In this paper, the system error e(t) and its change rate ec(t) are introduced into the contracting-expanding factor as dynamic parameters to realize the adaptive adjustment of the contracting-expanding factor parameters, and propose a variable universe fuzzy PID control based on dynamic adjustment functions (VUFP-DAF), which uses the real-time contracting-expanding factor to realize the adaptive adjustment of the fuzzy universe, so as to improve the ride comfort of vehicles. The research results show that the proposed VUFP-DAF has strong adaptability and can effectively improve the ride comfort and handling stability of vehicles under different speeds and road excitations, providing a certain technical basis for the development of the semi-active suspension system
Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2‑Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents
The
cellular antioxidant system plays key roles in blocking or
retarding the pathogenesis of adult neurodegenerative disorders as
elevated oxidative stress has been implicated in the pathophysiology
of such diseases. Molecules with the ability in enhancing the antioxidant
defense thus are promising candidates as neuroprotective agents. We
reported herein the synthesis of piperlongumine analogues and evaluation
of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced
neuronal cell oxidative damage in the neuron-like PC12 cells. The
structure–activity relationship was delineated after the cytotoxicity
and protection screening. Two compounds (<b>4</b> and <b>5</b>) displayed low cytotoxicity and confer potent protection
of PC12 cells from the oxidative injury via upregulation of a panel
of cellular antioxidant molecules. Genetically silencing the transcription
factor Nrf2, a master regulator of the cellular stress responses,
suppresses the cytoprotection, indicating the critical involvement
of Nrf2 for the cellular action of compounds <b>4</b> and <b>5</b> in PC12 cells
Metabolic Labeling of Legionaminic acid in Flagellin Glycosylation of Campylobacter jejuni Identifies Maf4 as a Putative Legionaminyl Transferase
Campylobacter jejuni is the major human food-borne pathogen. Its bipolar flagella are heavily O-glycosylated with microbial sialic acids and essential for its motility and pathogenicity. However, both the glycosylation of flagella and the exact contribution of legionaminic acid (Leg) to flagellar activity is poorly understood. Herein, we report the development of a metabolic labeling method for Leg glycosylation on bacterial flagella with probes based on azide-modified Leg precursors. The hereby azido-Leg labeled flagellin could be detected by Western blot analysis and imaged on intact bacteria. Using the probes on C. jejuni and its isogenic maf4 mutant we also further substantiated the identification of Maf4 as a putative Leg glycosyltransferase. Further evidence was provided by UPLC–MS detection of labeled CMP-Leg and an in silico model of Maf4. This method and the developed probes will facilitate the study of Leg glycosylation and the functional role of this modification in C. jejuni motility and invasiveness
Does tumor size have its prognostic role in colorectal cancer? Re-evaluating its value in colorectal adenocarcinoma with different macroscopic growth pattern
Metabolic Labeling of Legionaminic acid in Flagellin Glycosylation of Campylobacter jejuni Identifies Maf4 as a Putative Legionaminyl Transferase
Campylobacter jejuni is the major human food-borne pathogen. Its bipolar flagella are heavily O-glycosylated with microbial sialic acids and essential for its motility and pathogenicity. However, both the glycosylation of flagella and the exact contribution of legionaminic acid (Leg) to flagellar activity is poorly understood. Herein, we report the development of a metabolic labeling method for Leg glycosylation on bacterial flagella with probes based on azide-modified Leg precursors. The hereby azido-Leg labeled flagellin could be detected by Western blot analysis and imaged on intact bacteria. Using the probes on C. jejuni and its isogenic maf4 mutant we also further substantiated the identification of Maf4 as a putative Leg glycosyltransferase. Further evidence was provided by UPLC–MS detection of labeled CMP-Leg and an in silico model of Maf4. This method and the developed probes will facilitate the study of Leg glycosylation and the functional role of this modification in C. jejuni motility and invasiveness