Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, where one primary transcript yields six individual miRNAs. Here, we functionally dissected the individual components of mir-17-92 by assaying their tumorigenic potential in vivo. Using the Em-myc model of mouse B-cell lymphoma, we identified miR-19 as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. The oncogenic activity of miR-19 is at least in part due to its repression of the tumor suppressor Pten. Consistently, miR-19 activates the Akt-mTOR (mammalian target of rapamycin) pathway, thereby functionally antagonizing Pten to promote cell survival. Our findings reveal the essential role of miR-19 in mediating the oncogenic activity of mir-17-92, and implicate the functional diversity of mir-17-92 components as the molecular basis for its pleiotropic effects during tumorigenesis.

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Low levels of activity in hospital inpatients contribute to functional decline. Previous studies have shown low levels of activity in older inpatients, but few have investigated younger inpatients (aged <65 years). This observational study measured activity in older (aged ≥65 years) and younger hospital inpatients on 3 wards (medical, surgical, oncology) in a major teaching hospital in Brisbane, Australia, as part of a quality‐improvement intervention to enhance mobility. Using structured behavioral mapping protocols, participants were observed for 2‐minute intervals throughout 4, 4‐hour daytime observation periods. The proportion of time spent at different activity levels was calculated for each participant, and time spent standing, walking or wheeling was compared between age group and wards. There were 3272 observations collected on 132 participants (median, 30 per patient; range, 9–35). The most time was spent lying in bed (mean 57%), with 9% standing or walking. There were significant differences among wards, but no difference between older and younger subgroups. Low mobility is common in adult inpatients of all ages. Behavioral mapping provided measures suitable for use in quality improvement. Journal of Hospital Medicine 2016;11:289–291. © 2016 Society of Hospital Medicine

Programmed cell death is important for the proper development of the retina, and microRNAs (miRNAs) may be critical for its regulation. Here, we report that miR24a is expressed in the neural retina and is required for correct eye morphogenesis in Xenopus. Inhibition of miR-24a during development causes a reduction in eye size due to a significant increase in apoptosis in the retina, whereas overexpression of miR-24a is sufficient to prevent apoptosis. We show that miR-24a negatively regulates the proapoptotic factors caspase9 and apaf1, demonstrating a role for miRNAs in the regulation of apoptosis during normal development. Programmed cell death, or apoptosis, regulates the size and morphology of developing tissues and organs, and this is particularly true in the developing neural retina. The neural retina gives rise to the photoreceptors, retinal ganglion cells, and the optic nerve, and as many as 90% of newborn retinal ganglion cells die during rat retinal development (de la Rosa and de Pablo 2000;Vecino et al. 2004). In Xenopus, spatiotemporal elimination of retinal cells is a key factor in maturation (Gaze and Grant 1992). In the chick, Caspase-dependent apoptosis has been demonstrated in the retina, and inhibition of Caspases results in an enlargement of the ganglion cell layer (Mayordomo et al. 2003). Similarly, in mice, apoptotic factors are highly expressed in the early retina and downregulated as development proceeds (O'Driscoll et al. 2006;Wallace et al. 2006), and knockdown of Caspases results in an overgrown retina (Hakem et al. 1998). However, the factors important for the regulation of Caspases and other apoptotic factors in the eye are unknown, although some transcriptional regulation has been postulated (Wallace et al. 2006). microRNAs (miRNAs), a class of regulatory noncoding RNA genes, have evolutionarily conserved roles during the development of many organs, including the heart and nervous system (Zhao et al. 2005;Makeyev et al. 2007). miRNAs are transcribed by RNA Polymerase II as primary miRNAs (pri-miRNAs). These transcripts are then processed by the enzymes Drosha and Dicer to generate the mature single-stranded miRNA of ;22 nucleotides, which is then incorporated into the RNA-induced silencing complex (RISC), characterized by the presence of the Argonaute family of proteins (Pasquinelli et al. 2005). This complex is responsible for the regulatory function of the miRNAs, leading to translational repression or degradation of target mRNAs.Several miRNAs have been implicated in the regulation of apoptosis in Drosophila (Xu et al. 2004). In various forms of cancer, miR-21 has been shown to be an antiapoptotic factor (Chan et al. 2005;Cheng et al. 2005) and miR-34 has been shown to be a downstream target of p53 and an inducer of cell death (He et al. 2007). However, knowledge is still lacking about the in vivo roles of most miRNAs during vertebrate development. Recent work in mice has shown that Dicer inactivation, specifically in the retina, results in neuronal degeneration (Damiani et al. 20...

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Aqueous solutions of 5% and 10% trisodium phosphate (TSP), 0.1% and 0.5% cetylpyridinium chloride (CPC), 1% and 2% lactic acid (LA), and 0.1% and 0.5% grapefruit seed extract (DF-100) were evaluated in prechill spraying for reducing Salmonella typhimurium attached on chicken skins. Chicken skins were inoculated with S. typhimurium and then sprayed with the selected chemical solutions for 30 sec at 206 kPa and 20 degrees C. After chemical spraying, the skins were rinsed by spraying tap water for 30 sec. Each skin was stomached in buffered peptone water (BPW) for 1 min. The stomaching water was then diluted serially, inoculated onto both xylose lysine tergitol (XLT4) agar and Aerobic Plate Count (APC) Petrifilm, and incubated for 24 hr at 37 degrees C. The results showed that the numbers of Salmonella on the chicken skins after the chemical spraying were significantly lower than those without spray (P < 0.05). The CPC reduced Salmonella by 1.5 to 1.9 log10. TSP resulted in a 2.1 to 2.2 log10 reduction of Salmonella and DF-100 produced a 1.6 to 1.8 log10 reduction of Salmonella. The LA had a number of Salmonella with a 2.2 log10 reduction. The 0.5% CPC resulted a significantly greater reduction in Salmonella than 0.1% CPC. There were no significant differences in Salmonella reduction between different concentrations of the other three chemicals.