mRNAs can be targeted to specific neuronal subcellular domains, which enables rapid changes in the local proteome through local translation. This mRNA-based mechanism links extrinsic signals to spatially restricted cellular responses and can mediate stimulus-driven adaptive responses such as dendritic plasticity. Local mRNA translation also occurs in growing axons where it can mediate directional responses to guidance signals. Recent profiling studies have revealed that both growing and mature axons possess surprisingly complex and dynamic transcriptomes, thereby suggesting that axonal mRNA localization is highly regulated and has a role in a broad range of processes, a view that is increasingly being supported by new experimental evidence. Here, we review current knowledge on the roles and regulatory mechanisms of axonal mRNA translation and discuss emerging links to axon guidance, survival, regeneration and neurological disorders.
SummaryLocal protein synthesis plays a key role in regulating stimulus-induced responses in dendrites and axons. Recent genome-wide studies have revealed that thousands of different transcripts reside in these distal neuronal compartments, but identifying those with functionally significant roles presents a challenge. We performed an unbiased screen to look for stimulus-induced, protein synthesis-dependent changes in the proteome ofXenopus retinal ganglion cell (RGC) axons. The intermediate filament protein lamin B2 (LB2), normally associated with the nuclear membrane, was identified as an unexpected major target. Axonal ribosome immunoprecipitation confirmed translation of lb2 mRNA in vivo. Inhibition of lb2 mRNA translation in axons in vivo does not affect guidance but causes axonal degeneration. Axonal LB2 associates with mitochondria, and LB2-deficient axons exhibit mitochondrial dysfunction and defects in axonal transport. Our results thus suggest that axonally synthesized lamin B plays a crucial role in axon maintenance by promoting mitochondrial function.
This nation-wide seroprevalence of H. pylori infection in South Korea was 46.6%, which showed the transition from a developing country to a developed country. More studies on the epidemiological factors and the route of transmission of H. pylori infection should be warranted.
The prevalence of IBS in the Korean population is 6.6%, and the male:female ratio is similar. Also, IBS is more frequent in younger subjects. Irritable bowel syndrome subjects visited a physician mostly due to abdominal pain.
Most studies of bowel habits have been conducted in Western countries. This study was conducted to estimate the epidemiology of constipation and the discrepancy between self-reported constipation and bowel habits in Koreans. Telephone interviews regarding bowel habits were conducted with a total of 1029 individuals in Korea, 15 years of age or older. Subjects were given a questionnaire which asked about bowel symptoms, sociodemographic associations, laxative use, and physician visits. Of all subjects 95.6% had a defecation frequency of between three per week and three per day. The prevalence was 16.5% for self-reported constipation, 9.2% for functional constipation (FC), and 3.9% for constipation-predominant irritable bowel syndrome (IBS-C). Of subjects' self-reporting constipation, proportions of FC and IBS-C were 21.8% and 23.5%, respectively. Of subjects excluding self-reported constipation, the proportion of FC was 6.8%. Prevalences of self-reported constipation and IBS-C were higher in females than in males (P < 0.001). Of subjects' self-reporting constipation, 8.2% used laxatives. We conclude that constipation is a common problem in the general Korean population.
Author Contributions QZ and RDA designed the experiments. QZ performed the chemistry of nanoparticle production and physicochemical characterization, carried out the pharmacokinetics study and in vivo biodistribution of the nanoparticles, and performed the in vitro/in vivo ultrasonic drug uncaging experiments, with guidance from MA and assistance from JBW and AK. Cryo-TEM imaging was performed by MAB, RHC, and NHN. QZ and BCY performed the ultrasound imaging and ultrasonic nicardipine uncaging experiments and their analysis. TI and KFW designed and performed the ultra-high-speed optical imaging and passive cavitation detection of the nanoemulsions. QZ, BCY, and RDA prepared the figures and wrote the manuscript, with input and edits from all the authors.
Mast cells are activated leading to the raised levels of substance P & VIP in IBS-D patients. However, the correlation between mast cells and levels of substance P & VIP differs according to gender.
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