Effect of storage time on the silage quality and microbial community of mixed maize and faba bean in the Qinghai-Tibet Plateau

Tibetan Plateau is facing serious shortage of forage in winter and spring season due to its special geographical location. Utilization of forages is useful to alleviate the forage shortage in winter and spring season. Consequently, the current study was aimed to evaluate the influence of storage time on the silage quality and microbial community of the maize (Zea mays L.) and faba bean (Vicia faba L.) mixed silage at Qinghai-Tibet Plateau. Maize and faba bean were ensiled with a fresh weight ratio of 7:3, followed by 30, 60, 90, and 120 days of ensiling. The results showed the pH value of mixed silage was below 4.2 at all fermentation days. The LA (lactic acid) content slightly fluctuated with the extension of fermentation time, with 33.76 g/kg DM at 90 days of ensiling. The AA (acetic acid) and NH3-N/TN (ammonium nitrogen/total nitrogen) contents increased with the extension of fermentation time and no significantly different between 90 and 120 days. The CP (crude protein) and WSC (water soluble carbohydrate) contents of mixed silage decreased significantly (P < 0.05) with ensiling time, but the WSC content remained stable at 90 days. The Proteobacteria was the predominant phyla in fresh maize and faba bean, and Pseudomonas and Sphingomonas were the predominant genera. After ensiling, Lactobacillus was the prevalent genus at all ensiling days. The relative abundance of Lactococcus increased rapidly at 90 days of ensiling until 120 days of fermentation. Overall, the storage time significant influenced the silage fermentation quality, nutrient content, and microbial environment, and it remained stable for 90 days of ensiling at Qinghai-Tibet Plateau. Therefore, the recommended storage time of forage is 90 days in Qinghai-Tibet Plateau and other cool areas

A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression

As bona fide p53 transcriptional targets, miR-34 microRNAs (miRNAs) exhibit frequent alterations in many human tumor types and elicit multiple p53 downstream effects upon overexpression. Unexpectedly, miR-34 deletion alone fails to impair multiple p53-mediated tumor suppressor effects in mice, possibly due to the considerable redundancy in the p53 pathway. Here, we demonstrate that miR-34a represses HDM4, a potent negative regulator of p53, creating a positive feedback loop acting on p53. In a Kras-induced mouse lung cancer model, miR-34a deficiency alone does not exhibit a strong oncogenic effect. However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53-miR-34 feedback loop can enhance oncogenesis in a specific context. The importance of the p53/miR-34/HDM4 feedback loop is further confirmed by an inverse correlation between miR-34 and full-length HDM4 in human lung adenocarcinomas. In addition, human lung adenocarcinomas generate an elevated level of a short HDM4 isoform through alternative polyadenylation. This short HDM4 isoform lacks miR-34-binding sites in the 3' untranslated region (UTR), thereby evading miR-34 regulation to disable the p53-miR-34 positive feedback. Taken together, our results elucidated the intricate cross-talk between p53 and miR-34 miRNAs and revealed an important tumor suppressor effect generated by this positive feedback loop

MiR-34 miRNAs provide a barrier for somatic cell reprogramming

Somatic reprogramming induced by defined transcription factors is a low-efficiency process that is enhanced by p53 deficiency. So far, p21 is the only p53 target shown to contribute to p53 repression of iPSC (induced pluripotent stem cell) generation, indicating that additional p53 targets may regulate this process. Here, we demonstrate that miR-34 microRNAs (miRNAs), particularly miR-34a, exhibit p53-dependent induction during reprogramming. Mir34a deficiency in mice significantly increased reprogramming efficiency and kinetics, with miR-34a and p21 cooperatively regulating somatic reprogramming downstream of p53. Unlike p53 deficiency, which enhances reprogramming at the expense of iPSC pluripotency, genetic ablation of Mir34a promoted iPSC generation without compromising self-renewal or differentiation. Suppression of reprogramming by miR-34a was due, at least in part, to repression of pluripotency genes, including Nanog, Sox2 and Mycn (also known as N-Myc). This post-transcriptional gene repression by miR-34a also regulated iPSC differentiation kinetics. miR-34b and c similarly repressed reprogramming; and all three miR-34 miRNAs acted cooperatively in this process. Taken together, our findings identified miR-34 miRNAs as p53 targets that play an essential role in restraining somatic reprogramming. © 2011 Macmillan Publishers Limited. All rights reserved