Cancer vaccination may be our best and most benign option for preventing or treating metastatic cancer. However, breakthroughs are hampered by immune suppression in the tumor microenvironment. In this study, we analyzed whether cyclic diguanylate (c-di-GMP), a ligand for stimulator of interferon genes (STING), could overcome immune suppression and improve vaccination against metastatic breast c...

The effect of feed protein type on body composition and growth has been examined. Evidence exists that whey protein concentrate is effective at limiting body fat expansion. The presence of caseinomacropeptide, a mixture of glycosylated and non-glycosylated carbohydrate residues, in particular glycomacropeptide (GMP) in whey protein concentrate may be important for this effect. The influence of ...

BACKGROUND To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe. OBJECTIVE W...

GMP-140 is an integral membrane glycoprotein of apparent Mr = 140,000 located in secretory storage granules of platelets and vascular endothelial cells. When these cells are activated, GMP-140 redistributes from the membrane of the granules to the plasma membrane. To gain insight into the potential function of GMP-140, we examined aspects of its structure and biosynthesis. The amino acid compos...

Innate immunity is the primary mechanism by which extracellular bacterial pathogens are effectively cleared from the lung. We have previously shown that cyclic di-GMP (c-di-GMP [c-diguanylate]) is a novel small molecule immunomodulator and immunostimulatory agent that triggers protective host innate immune responses. Using a murine model of bacterial pneumonia, we show that local intranasal (i....

Bacteria have various ways to sense environmental signals and to adapt their behavior and physiology through different signaling systems. Secondary messenger signaling, amplified by enzymatic activity, rapidly transmits a signal in the cell resulting in allosteric functional control. Cyclic diguanosine monophosphate (c-di-GMP) is a novel global secondary messenger, that is found exclusively in ...

Biofilms formed by bacterial pathogens are responsible of more than 70% of all infections in developed countries and are less sensitive to treatments with antimicrobial agents. The ubiquitous second messenger 3', 5'-cyclic diguanylic acid (c-di-GMP) is used in most bacteria to control the switch to the biofilm lifestyle; c-di-GMP has no counterpart in eukaryotic cells and thus it is an ideal ta...

The bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) signaling pathway regulates biofilm formation, virulence, and other processes in many bacterial species and is critical for their survival. Two classes of c-di-GMP-binding riboswitches have been discovered that bind this second messenger with high affinity and regulate diverse downstream genes, underscoring the importance of RNA ...

In recent years, the potential of glycosylated food components to positively influence health has received considerable attention. Milk is a rich source of biologically active glycoconjugates which are associated with antimicrobial, immunomodulatory, anti-adhesion, anti-inflammatory and prebiotic properties. Glycomacropeptide (GMP) is the C-terminal portion of kappa-casein that is released from...

Upon Salmonella enterica serovar Typhimurium infection of the gut, an early line of defense is the gastrointestinal epithelium which senses the pathogen and intrusion along the epithelial barrier is one of the first events towards disease. Recently, we showed that high intracellular amounts of the secondary messenger c-di-GMP in S. typhimurium inhibited invasion and abolished induction of a pro...