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In LPS biosynthesis pathway, lpxA, lpxC, KdsA, KdsB and gmhA were considered as valid targets for drug development. Enzymes lpxA and lpxC (catalyzes committed step) contribute to the formation of lipid A which is a conserved core oligosaccharide region of LPS molecules. Lipid A is responsible for toxic effects of gram-negative bacterial infection. The target protein KdsB (CMP-Kdo synthetase) is unique in its direct coupling of KDO (sugar) to cytosine monophosphate (CMP) in KDO biosynthesis which is a part of LPS inner core. Another druggable protein obtained in this pathway is gmhA (lpcA) that catalyzes the first step in biosynthesis of ADP-L-glycero-D-manno heptose [ 48 ]. Inhibiting gmhA would create heptose less core LPS leading to enhanced sensitivity of F. nucleatum to even low concentration of novobiocin, detergents and bile salts [ Sheer Wrap Baron by VIDA VIDA Visa Payment Cheap Online i8XCQ9

Prediction of subcellular localization of druggable targets using various online servers delineated that 29 out of 35 target proteins were located in cytoplasm while the rest were in membrane (Additional file Shopping Online Cheap Price SUITS AND JACKETS Waistcoats Harris Tweed Sale Footlocker Pictures Visa Payment Cheap Online Discount Official vh5qL
: Table S7). Cytoplasmic proteins can be considered for small molecule drug development while membrane or secreted proteins for vaccine development.

Fig. 2

Biological network of host-pathogen protein-protein interactions are shown using Cytoscape. and host interacting proteins are represented in pink and blue color respectively

If a set of proteins are significantly enriched in certain biological processes or pathways, they are likely to play similar role in vivo [ 50 ]. Hence, pathway, functional, disease enrichment analysis and functional annotation clustering were carried out to assess predicted HP-PPIs using Database for Annotation, Visualization and Integrated Discovery (DAVID) [ 51 ]. This analysis resulted in significantly enriched 45 pathways, 306 gene ontology (GO) terms and 21 diseases with minimum count of three gene set and p-value lower than 0.05 in addition to 47 annotation clusters with cut-off enrichment score of > 1 and minimum of three terms.

This analysis was performed based on the assessment that host proteins involved in HPIs possess functional correlation to the pathways that are relevant to pathogen’s infection. Among the obtained pathways from DAVID Functional Annotation Chart analysis, Wnt signaling pathway, ECM-receptor interactions, focal adhesion, toll-like receptor (TLR) signaling and CRC probably suggest the role of F. nucleatum in adhesion, invasion into epithelial cells and triggering of signal transduction pathways that promote CRC [ 1 , 11 , 26 , 52 ]. Other attained pathways such as T-cell, B-cell receptor signaling, T-cell, B-cell activation, antigen processing and presentation, Lck and Fyn tyrosine kinases in initiation of TCR activation, viral myocarditis indicate the relevance of F. nucleatum infection to host immune responses [ 11 , Foldaway Tote Crazy Christmas Trees by VIDA VIDA For Sale Very Cheap Enjoy For Sale For Sale Best Sale For Sale Discount Pre Order onFEMGA
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55 ]. F. nucleatum infection inhibits T-cell activation by preventing cells to exit G0/G1 phase of cell cycle which may result in local and/or systemic immunosuppression [ Buy Cheap From China Womens Quilted Bucket Hat Betmar Marketable Online jtsLgbd3V
]. Chronic inflammation in periodontal diseases due to F. nucleatum has been reported as potential risk factor for Alzheimer’s disease [ 56 ]. Most of the obtained pathways were in accordance to literature reports while the rest of them could be either false positive or may have an indirect effect which seeks further experimental support. This include renal cell, basal cell, small cell lung, non-small cell lung, endometrial, thyroid, pancreatic, acute myeloid leukemia, glioma, leukocyte transendothelial migration and melanoma.

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Health advocates are urging incoming college students to get a new meningitis vaccine.

Health advocates are urging incoming college students to get a new meningitis vaccine.

(Dreamstime / TNS)
Michele Munz St. Louis Post-Dispatch

As young adults head off to college and into close quarters with others in dorms, cafeterias and classrooms, health advocates urge students and their parents to consider a new vaccine that may not be on their radar.

The meningitis B vaccine, federally approved in late 2014, can protect against most B strains of the disease, which account for about 50 percent of all meningitis cases in young adults.

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Meningitis is a highly contagious bacterial disease that starts with flu-like symptoms of fever, fatigue and body aches. Teenagers and college students living in close quarters are high-risk groups for the disease. It can be spread by sharing things like cups, utensils, cigarettes and lipstick.

It can be treated with antibiotics if caught early, but can escalate quickly to swelling of the brain and spinal cord. While only about 1,000 people in the U.S. get meningitis each year, it leads to death in 10 percent to 15 percent of cases and can cause permanent brain damage, hearing loss and loss of limbs.

“It takes so little to be protected against it and the effects of meningitis are just so devastating, so why risk it?” said Jill Thompson, director of strategic initiative at Generate Health, a St. Louis regional coalition of organizations and advocates working to improve health.

The coalition has created a toolkit to help area college and universities educate students about meningitis, which includes sample letters to parents and students, informational graphics and social media tools.

“We do a lot to keep all those working in the immunization field up to date with this ever-changing field,” Thompson said, especially in the area of meningitis.

Many families are just becoming familiar with the combination meningitis vaccine which protects against the A, C, W and Y strains. It involves a shot around age 11 and then a booster dose after age 16.

Missouri legislation took effect before the 2015-2016 school year requiring every public university student living on campus to get the combination vaccine.

Starting last school year, students entering the eighth and 12th grades in Missouri are also required to have the vaccine. Illinois started requiring it for sixth- and 12th-graders in 2015.

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