scholarly journals Structural and Biochemical Analyses Reveal that Chlorogenic Acid Inhibits the Shikimate Pathway

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Neetu Neetu ◽  
Madhusudhanarao Katiki ◽  
Aditya Dev ◽  
Stuti Gaur ◽  
Shailly Tomar ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Antibacterial Properties ◽  
Shikimate Pathway ◽  
Titration Calorimetry ◽  
Binary Complex ◽  
Content Type ◽  
Providencia Alcalifaciens ◽  
Wide Range ◽  
Inhibition Studies ◽  
Dehydroquinate Synthase

ABSTRACT Chlorogenic acid (CGA) is a phenolic compound with well-known antibacterial properties against pathogens. In this study, structural and biochemical characterization was used to show the inhibitory role of CGA against the enzyme of the shikimate pathway, a well-characterized drug target in several pathogens. Here, we report the crystal structures of dehydroquinate synthase (DHQS), the second enzyme of the shikimate pathway, from Providencia alcalifaciens (PaDHQS), in binary complex with NAD and ternary complex with NAD and CGA. Structural analyses reveal that CGA occupies the substrate position in the active site of PaDHQS, which disables domain movements, leaving the enzyme in an open and catalysis-incompetent state. The binding analyses by isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) show that CGA binds to PaDHQS with KD (equilibrium dissociation constant) values of 6.3 μM and 0.5 μM, respectively. In vitro enzyme inhibition studies show that CGA inhibits PaDHQS with a Ki of 235 ± 21 μM, while it inhibits the growth of Providencia alcalifaciens, Moraxella catarrhalis, Staphylococcus aureus, and Escherichia coli with MIC values of 60 to 100 μM. In the presence of aromatic amino acids supplied externally, CGA does not show the toxic effect. These results, along with the observations of the inhibition of the 3-deoxy-d-arabino-heptulosonate-7-phosphate (DAHP) regulatory domain by CGA in our previous study, suggest that CGA binds to shikimate pathway enzymes with high affinity and inhibits their catalysis and can be further exploited for designing novel drug-like molecules. IMPORTANCE The shikimate pathway is an attractive target for the development of herbicides and antimicrobial agents, as it is essential in plants, bacteria, and apicomplexan parasites but absent in humans. The enzymes of shikimate pathway are conserved among bacteria. Thus, the inhibitors of the shikimate pathway act on wide range of pathogens. We have identified that chlorogenic acid targets the enzymes of the shikimate pathway. The crystal structure of dehydroquinate synthase, the second enzyme of the pathway, in complex with chlorogenic acid and enzymatic inhibition studies explains the mechanism of inhibition of chlorogenic acid. These results suggest that chlorogenic acid has a good chemical scaffold and have important implications for its further development as a potent inhibitor of shikimate pathway enzymes.

scholarly journals Genomic Insights into Adaptations of Trimethylamine-Utilizing Methanogens to Diverse Habitats, Including the Human Gut

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jacobo de la Cuesta-Zuluaga ◽  
Tim D. Spector ◽  
Nicholas D. Youngblut ◽  
Ruth E. Ley
Keyword(s):  
Cardiovascular Disease ◽  
Environmental Samples ◽  
Shikimate Pathway ◽  
Human Populations ◽  
Human Gut ◽  
Host Genotype ◽  
Content Type ◽  
Wide Range ◽  
Bile Resistance ◽  
Methylated Amines

ABSTRACT Archaea of the order Methanomassiliicoccales use methylated amines such as trimethylamine as the substrates for methanogenesis. They form two large phylogenetic clades and reside in diverse environments, from soil to the human gut. Two genera, one from each clade, inhabit the human gut: Methanomassiliicoccus, which has one cultured representative, and “Candidatus Methanomethylophilus,” which has none. Questions remain regarding their distribution across biomes and human populations, their association with other taxa in the gut, and whether host genetics correlate with their abundance. To gain insight into the Methanomassiliicoccales clade, particularly its human-associated members, we performed a genomic comparison of 72 Methanomassiliicoccales genomes and assessed their presence in metagenomes derived from the human gut (n = 4,472, representing 22 populations), nonhuman animal gut (n = 145), and nonhost environments (n = 160). Our analyses showed that all taxa are generalists; they were detected in animal gut and environmental samples. We confirmed two large clades, one enriched in the gut and the other enriched in the environment, with notable exceptions. Genomic adaptations to the gut include genome reduction and genes involved in the shikimate pathway and bile resistance. Genomic adaptations differed by clade, not habitat preference, indicating convergent evolution between the clades. In the human gut, the relative abundance of Methanomassiliicoccales spp. correlated with trimethylamine-producing bacteria and was unrelated to host genotype. Our results shed light on the microbial ecology of this group and may help guide Methanomassiliicoccales-based strategies for trimethylamine mitigation in cardiovascular disease. IMPORTANCE Methanomassiliicoccales are less-known members of the human gut archaeome. Members of this order use methylated amines, including trimethylamine, in methane production. This group has only one cultured representative; how its members adapted to inhabit the mammalian gut and how they interact with other microbes is largely unknown. Using bioinformatics methods applied to DNA from a wide range of samples, we profiled the abundances of these Archaea spp. in environmental and host-associated microbial communities. We observed two groups of Methanomassiliicoccales, one largely host associated and one largely found in environmental samples, with some exceptions. When host associated, these Archaea have smaller genomes and possess genes related to bile resistance and aromatic amino acid precursors. We did not detect Methanomassiliicoccales in all human populations tested, but when present, they were correlated with bacteria known to produce trimethylamine. Due to their metabolism of trimethylamine, these intriguing Archaea may form the basis of novel therapies for cardiovascular disease.

Anti-diabetic and anti-proliferative activities of herbal teas, Athrixia phylicoides DC and Monsonia burkeana Planch. ex Harv, indigenous to South Africa

2019 ◽  
Vol 121 (4) ◽  
pp. 964-974 ◽  
Author(s):  
Lutendo Patricia Mathivha ◽  
Vuyisile Samuel Thibane ◽  
Fhatuwani Nixwell Mudau
Keyword(s):  
Cervical Cancer ◽  
Hela Cell ◽  
Chlorogenic Acid ◽  
Cell Line ◽  
Phenolic Content ◽  
Antioxidant Activities ◽  
Hela Cell Line ◽  
Content Type ◽  
Wide Range ◽  
Athrixia Phylicoides

Purpose The purpose of this paper is to investigate the health and medicinal importance of bush tea (Athrixia phylicoides DC) and special tea (Monsonia burkeana Planch. ex Harv), two of Southern African indigenous herbal teas. Design/methodology/approach The two herbal teas, A. phylicoides and M. burkeana were extracted individually and in combined ratios for analysis. The phenolic content was determined and the different phenolic compounds were identified using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The anti-diabetic activity of the teas was determined by evaluating the inhibition of both α-amylase and α-glucosidase in vitro. The anti-proliferative activity was measured on human cervical cancer (HeLa) cell line using the MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium) assay. Findings Gallic acid, chlorogenic acid and quercetin were identified to be present in significant quantities by TLC. The HPLC quantified the presence of catechin (1.567 mg/g) and chlorogenic acid (1.862 mg/g) in special tea while chlorogenic acid (1.288 mg/g) was present in bush tea. Bush tea and special tea expressed significant levels of phenolic content and high antioxidant activities. Special tea (S100) expressed high inhibition of α-amylase, α-glucosidase and HeLa cell line proliferation when compared to bush tea (B100). Originality/value Both bush tea and special tea could provide an alternative for treatment and management of both diabetes and cervical cancer. However, future studies are needed to investigate their synergistic effect with a wide range of other commercial herbal teas.

scholarly journals Transfer of Plasmid DNA to Clinical Coagulase-Negative Staphylococcal Pathogens by Using a Unique Bacteriophage

2015 ◽  
Vol 81 (7) ◽  
pp. 2481-2488 ◽  
Author(s):  
Volker Winstel ◽  
Petra Kühner ◽  
Bernhard Krismer ◽  
Andreas Peschel ◽  
Holger Rohde
Keyword(s):  
Plasmid Dna ◽  
Genetic Manipulation ◽  
Current Knowledge ◽  
Virulence Determinants ◽  
Coagulase Negative Staphylococci ◽  
Reliable Technique ◽  
Content Type ◽  
Research Activities ◽  
Wide Range ◽  
Genetic Barriers

ABSTRACTGenetic manipulation of emerging bacterial pathogens, such as coagulase-negative staphylococci (CoNS), is a major hurdle in clinical and basic microbiological research. Strong genetic barriers, such as restriction modification systems or clustered regularly interspaced short palindromic repeats (CRISPR), usually interfere with available techniques for DNA transformation and therefore complicate manipulation of CoNS or render it impossible. Thus, current knowledge of pathogenicity and virulence determinants of CoNS is very limited. Here, a rapid, efficient, and highly reliable technique is presented to transfer plasmid DNA essential for genetic engineering to important CoNS pathogens from a uniqueStaphylococcus aureusstrain via a specificS. aureusbacteriophage, Φ187. Even strains refractory to electroporation can be transduced by this technique once donor and recipient strains share similar Φ187 receptor properties. As a proof of principle, this technique was used to delete the alternative transcription factor sigma B (SigB) via allelic replacement in nasal and clinicalStaphylococcus epidermidisisolates at high efficiencies. The described approach will allow the genetic manipulation of a wide range of CoNS pathogens and might inspire research activities to manipulate other important pathogens in a similar fashion.

scholarly journals Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Susan L. Brockmeier ◽  
Crystal L. Loving ◽  
Tracy L. Nicholson ◽  
Jinhong Wang ◽  
Sarah E. Peters ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Trial ◽  
Streptococcus Suis ◽  
Protein Subunit ◽  
Content Type ◽  
Degree Of Protection ◽  
Wide Range ◽  
Associated Proteins ◽  
Clinical Protection ◽  
Cellular Immune

ABSTRACT Streptococcus suis is a bacterium that is commonly carried in the respiratory tract and that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities, efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent S. suis . While subunit vaccination with the S. suis proteins induced IgG antibodies to each individual protein and a cellular immune response to the pool of proteins and provided substantial protection from challenge with virulent S. suis , the immune response elicited and the degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different S. suis serotypes, indicating a potential for cross protection.

scholarly journals Nanometals-Containing Polymeric Membranes for Purification Processes

Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 513
Author(s):  
Anna Rabajczyk ◽  
Maria Zielecka ◽  
Krzysztof Cygańczuk ◽  
Łukasz Pastuszka ◽  
Leszek Jurecki
Keyword(s):  
Synergistic Effects ◽  
Membrane Surface ◽  
Antibacterial Properties ◽  
Polymeric Membranes ◽  
Treatment Processes ◽  
Wide Range ◽  
Different Types ◽  
Type Size ◽  
Titanium Zinc ◽  
Membrane Surface Charge

A recent trend in the field of membrane research is the incorporation of nanoparticles into polymeric membranes, which could produce synergistic effects when using different types of materials. This paper discusses the effect of the introduction of different nanometals such as silver, iron, silica, aluminum, titanium, zinc, and copper and their oxides on the permeability, selectivity, hydrophilicity, conductivity, mechanical strength, thermal stability, and antiviral and antibacterial properties of polymeric membranes. The effects of nanoparticle physicochemical properties, type, size, and concentration on a membrane’s intrinsic properties such as pore morphology, porosity, pore size, hydrophilicity/hydrophobicity, membrane surface charge, and roughness are discussed, and the performance of nanocomposite membranes in terms of flux permeation, contaminant rejection, and antifouling capability are reviewed. The wide range of nanocomposite membrane applications including desalination and removal of various contaminants in water-treatment processes are discussed.

The role of organizational culture in the knowledge management process

2015 ◽  
Vol 19 (3) ◽  
pp. 433-455 ◽  
Author(s):  
Christina Ling-hsing Chang ◽  
Tung-Ching Lin
Keyword(s):  
Organizational Culture ◽  
Knowledge Management ◽  
Customer Service ◽  
Survey Methodology ◽  
Cultural Dimensions ◽  
Content Type ◽  
Knowledge Resources ◽  
Positive Effects ◽  
Wide Range ◽  
The Individual

Purpose – The purpose of the study is to focus on the enhancement of knowledge management (KM) performance and the relationship between organizational culture and KM process intention of individuals because of the diversity of organizational cultures (which include results-oriented, tightly controlled, job-oriented, closed system and professional-oriented cultures). Knowledge is a primary resource in organizations. If firms are able to effectively manage their knowledge resources, then a wide range of benefits can be reaped such as improved corporate efficiency, effectiveness, innovation and customer service. Design/methodology/approach – The survey methodology, which has the ability to enhance generalization of results (Dooley, 2001), was used to collect the data utilized in the testing of the research hypotheses. Findings – Results- and job-oriented cultures have positive effects on employee intention in the KM process (creation, storage, transfer and application), whereas a tightly controlled culture has negative effects. Research limitations/implications – However, it would have been better to use a longitudinal study to collect useful long-term data to understand how the KM process would be influenced when organizational culture dimensions are changed through/by management. This is the first limitation of this study. According to Mason and Pauleen (2003), KM culture is a powerful predictor of individual knowledge-sharing behavior, which is not included in this study. Thus, this is the second limitation of this paper. Moreover, national culture could be an important issue in the KM process (Jacks et al., 2012), which is the third limitation of this paper for not comprising it. Practical implications – In researchers’ point of view, results- and job-oriented cultures have positive effects, whereas a tightly controlled culture has a negative effect on the KM process intention of the individual. These findings provide evidences that challenge the perspective of Kayworth and Leidner (2003) on this issue. As for practitioners, management has a direction to modify their organizational culture to improve the performance of KM process. Social implications – Both behavioral and value perspectives of the organizational cultural dimensions (results-oriented, tightly control, job-oriented, sociability, solidarity, need for achievement and democracy) should be examined to ascertain their effects firstly on KM culture and then on the KM process intention of the individual. It is hoped that the current study will spawn future investigations that lead to the development of an integrated model which includes organizational culture, KM culture and the KM process intention of the individual. Originality/value – The results-oriented, loosely controlled and job-oriented cultures will improve the effectiveness of the KM process and will also increase employees’ satisfaction and willingness to stay with the organization.

From digital citizen to digital professional

Kybernetes ◽  
2019 ◽  
Vol 48 (7) ◽  
pp. 1463-1477
Author(s):  
Olga Marino ◽  
Jaime Andres Gutierrez ◽  
Sandra Aguirre
Keyword(s):  
Information And Communication Technologies ◽  
Communication Technologies ◽  
Cutting Edge ◽  
Case Study Methodology ◽  
Content Type ◽  
Innovative Strategy ◽  
Global Issues ◽  
Wide Range ◽  
Information And Communication ◽  
Teaching Learning

Purpose This paper aims to propose and evaluate a pedagogically sound and innovative strategy to teach a higher education course that prepares future professionals to intelligently use information and communication technologies (ICTs) in their personal and professional lives. Design/methodology/approach The conceptual framework used for the design of the course was the socio-constructivism and activity theories. The implementation of the course was evaluated using the intrinsic case study methodology by including several instruments. Findings The pedagogical strategy proposed proved to be sound, as the evaluation showed that students were able to describe, use and propose innovative uses of a wide range of cutting-edge technologies in their both everyday lives and professional settings; they also had the skills to analyse the opportunities and challenges that these presented. Moreover, students liked this innovative way of learning and ended with a positive attitude towards ICT. Originality/value Although several courses prepare students to be digital citizens or use ICT to enhance the teaching-learning process, millennials are ill prepared to use cutting-edge technologies in an innovative, responsible and critical way in their future professions. The course that was designed is original in that it goes beyond preparing digital citizens to prepare professionals in any domain to use ICT in an informed and responsible way. Moreover, it is a documented, successful example of an undergraduate universal course in a highly important current society dimension. The authors believe that its pedagogical proposal could be transferred to courses dealing with other global issues such as the environment, economy and peace.

Incompressible smoothed particle hydrodynamics for MHD double-diffusive natural convection of a nanofluid in a cavity containing an oscillating pipe

2019 ◽  
Vol 30 (2) ◽  
pp. 882-917 ◽  
Author(s):  
Abdelraheem M. Aly
Keyword(s):  
Natural Convection ◽  
Smoothed Particle Hydrodynamics ◽  
Cavity Wall ◽  
Lagrangian Description ◽  
Content Type ◽  
Wide Range ◽  
Particle Hydrodynamics ◽  
Smoothed Particle ◽  
Incompressible Smoothed Particle Hydrodynamics ◽  
Double Diffusive

Purpose This paper aims to adopt incompressible smoothed particle hydrodynamics (ISPH) method to simulate MHD double-diffusive natural convection in a cavity containing an oscillating pipe and filled with nanofluid. Design/methodology/approach The Lagrangian description of the governing partial differential equations are solved numerically using improved ISPH method. The inner oscillating pipe is divided into two different pipes as an open and a closed pipe. The sidewalls of the cavity are cooled with a lower concentration C_c and the horizontal walls are adiabatic. The inner pipe is heated with higher concentration C_h. The analysis has been conducted for the two different cases of inner oscillating pipes under the effects of wide range of governing parameters. Findings It is found that a suitable oscillating pipe makes a well convective transport inside a cavity. Presence of the oscillating pipe has effects on the heat and mass transfer and fluid intensity inside a cavity. Hartman parameter suppresses the velocity and weakens the maximum values of the stream function. An increase on Hartman, Lewis and solid volume fraction parameters leads to an increase on average Nusselt number on an oscillating pipe and left cavity wall. Average Sherwood number on an oscillating pipe and left cavity wall decreases as Hartman parameter increases. Originality/value The main objective of this work is to study the MHD double-diffusive natural convection of a nanofluid in a square cavity containing an oscillating pipe using improved ISPH method.

scholarly journals Synthesis, Structural, Morphological and Thermal Characterization of Five Different Silica-Polyethylene Glycol-Chlorogenic Acid Hybrid Materials

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1586
Author(s):  
Michelina Catauro ◽  
Pavel Šiler ◽  
Jiří Másilko ◽  
Roberta Risoluti ◽  
Stefano Vecchio Ciprioti
Keyword(s):  
Polyethylene Glycol ◽  
Chlorogenic Acid ◽  
Hybrid Materials ◽  
Sol Gel ◽  
Antibacterial Properties ◽  
Silica Matrix ◽  
Sem Images ◽  
Fixed Amount ◽  
Organic Components ◽  
Free Material

The present study investigated the structure, morphology, thermal behavior, and bacterial growth analysis of novel three-component hybrid materials synthesized by the sol-gel method. The inorganic silica matrix was weakly bonded to the network of two organic components: a well-known polymer such as polyethylene glycol (PEG, average molar mass of about 4000 g/mol), and an antioxidant constituted by chlorogenic acid (CGA). In particular, a first series was made by a 50 wt% PEG-based (CGA-free) silica hybrid along with two 50 wt% PEG-based hybrids containing 10 and 20 wt% of CGA (denoted as SP50, SP50C10 and SP50C20, respectively). A second series contained a fixed amount of CGA (20 wt%) in silica-based hybrids: one was the PEG-free material (SC20) and the other two contained 12 and 50 wt% of PEG, respectively (SP12C20 and SP50C20, respectively), being the latter already included in the first series. The X-ray diffraction (XRD) patterns and scanning electron microscope (SEM) images of freshly prepared materials confirmed that all the materials were amorphous and homogeneous regardless of the content of PEG or CGA. The thermogravimetric (TG) analysis revealed a higher water content was adsorbed into the two component hybrids (SP50 and SC20) because of the availability of a larger number of H-bonds to be formed with water with respect to those of silica/PEG/CGA (SPC), where silica matrix was involved in these bonds with both organic components. Conversely, the PEG-rich materials (SP50C10 and SP50C20, both with 50 wt% of the polymer) retained a lower content of water. Decomposition of PEG and CGA occurred in almost the same temperature interval regardless of the content of each organic component. The antibacterial properties of the SiO2/PEG/CGA hybrid materials were studied in pellets using either Escherichia coli and Enterococcus faecalis, respectively. Excellent antibacterial activity was found against both bacteria regardless of the amount of polymer in the hybrids.

Numerical investigation of anguilliform locomotion by the SPH method

2019 ◽  
Vol 30 (1) ◽  
pp. 328-346 ◽  
Author(s):  
Amin Rahmat ◽  
Hossein Nasiri ◽  
Marjan Goodarzi ◽  
Ehsan Heidaryan
Keyword(s):  
Drag Coefficient ◽  
Numerical Investigation ◽  
Sph Method ◽  
Content Type ◽  
Aquatic Locomotion ◽  
Wide Range ◽  
Particle Hydrodynamics ◽  
Dummy Particles ◽  
Smoothed Particle ◽  
Sph Algorithm

Purpose This paper aims to introduce a numerical investigation of aquatic locomotion using the smoothed particle hydrodynamics (SPH) method. Design/methodology/approach To model this problem, a simple improved SPH algorithm is presented that can handle complex geometries using updatable dummy particles. The computational code is validated by solving the flow over a two-dimensional cylinder and comparing its drag coefficient for two different Reynolds numbers with those in the literature. Findings Additionally, the drag coefficient and vortices created behind the aquatic swimmer are quantitatively and qualitatively compared with available credential data. Afterward, the flow over an aquatic swimmer is simulated for a wide range of Reynolds and Strouhal numbers, as well as for the amplitude envelope. Moreover, comprehensive discussions on drag coefficient and vorticity patterns behind the aquatic are made. Originality/value It is found that by increasing both Reynolds and Strouhal numbers separately, the anguilliform motion approaches the self-propulsion condition; however, the vortices show different pattern with these increments.

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