O-linked β-N-acetylglucosamine (O-GlcNAc) modification regulates the activity of hundreds of nucleocytoplasmic proteins involved in a wide variety of cellular processes, such as gene expression, signaling, and cell growth; however, the mechanism underlying the regulation of B cell development and function by O-GlcNAcylation remains largely unknown. Here, we demonstrate that changes in cellular O-GlcNAc levels significantly affected the growth of pre-B cells, which rapidly proliferate to allow expansion of functional clones that express successfully rearranged heavy chains at the pro-B stage during early B cell development. In our study, the overall O-GlcNAc levels in these proliferative pre-B cells, which are linked to the glucose uptake rate, were highly induced when compared with those in pro-B cells. Thus, pharmacologically, genetically, or nutritionally, inhibition of O-GlcNAcylation in pre-B cells markedly downregulated c-Myc expression, resulting in cell cycle arrest via blockade of cyclin expression. Importantly, the population of B cells after the pro-B cell stage in mouse bone marrow was severely impaired by the administration of an O-GlcNAc inhibitor. These results strongly suggest that O-GlcNAcylation-dependent expression of c-Myc represents a new regulatory component of pre-B cell proliferation, as well as a potential therapeutic target for the treatment of pre-B cell-derived leukemia.
Yeasts are very useful microorganisms that are used in many industrial fermentation processes such as food and alcohol production. Microbial contamination of such processes is inevitable, since most of the fermentation substrates are not sterile. Contamination can cause a reduction of the final product concentration and render industrial yeast strains unable to be reused. Alternative approaches to controlling contamination, including the use of antibiotics, have been developed and proposed as solutions. However, more efficient and industry-friendly approaches are needed for use in industrial applications. This review covers: (i) general information about industrial uses of yeast fermentation, (ii) microbial contamination and its effects on yeast fermentation, and (iii) currently used and suggested approaches/strategies for controlling microbial contamination at the industrial and/or laboratory scale.
Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of posttranslational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells. The protective effect of O-GlcNAc inhibition for Stx-mediated pathogenic responses was also verified using three-dimensional (3D)cultured spheroids or organoids mimicking the human kidney. Treatment with an O-GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O-GlcNAcylation-dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O-GlcNAcylation is a potential approach to treat Stx-mediated diseases.
Although several Edwardsiella tarda infections have been reported, its
pathogenic role in marine mammals has not been investigated at the genome level. We
investigated the genome of E. tarda strain KC-Pc-HB1, isolated from the
false killer whale (Pseudorca crassidens) found bycaught in South Korea.
The obtained genome was similar to that of human pathogenic E. tarda
strains, but distinct from other Edwardsiella species. Although type III
and VI secretion systems, which are essential for the virulence of other
Edwardsiella species, were absent, several virulence-related genes
involved in the pathogenesis of E. tarda were found in the genome. These
results provide important insights into the E. tarda infecting marine
mammals and give valuable information on potential virulence factors in this pathogen.
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