METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.

The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.

The relationship between species richness and evenness in plant communities along a successional gradient: a study from sub-alpine meadows of the Eastern Qinghai-Tibetan Plateau, China.

The relationship between species richness and evenness across communities remains an unsettled issue in ecology from both theoretical and empirical perspectives. As a result, we do not know the mechanisms that could generate a relationship between species richness and evenness, and how this responds to spatial scale. Here we examine the relationship between species richness(S) and evenness (Pielou's J' evenness) using a chronosequence of successional sub-alpine meadow communities in the eastern Qinghai-Tibetan Plateau. These meadows range from natural community (never farmed), to those that have been protected from agricultural exploitation for periods ranging from 1 to 10 years. A total of 30 sampling quadrats with size of 0.5 m×0.5 m were laid out along two transects at each meadow. Using correlation analyses we found a consistent negative correlation between S and J' in these communities along the successional gradient at the sampling scale of 0.5 m×0.5 m. We also explored the relationship between S and J' at different sampling scales (from 0.5 m×0.5 m to10 m×10 m) using properly measured ramet-mapped data of a10 m×10 m quadrat in the natural community. We found that S was negatively corrected with J' at the scales of 0.5 m×0.5 m to 2 m×2 m, but such a relationships disappeared at relative larger scales (≥2 m×4 m). When fitting different species abundance models combined with trait-specific methods, we found that niche preemption may be the determining mechanism of species evenness along the succession gradient. Considering all results together, we can conclude that such niche differentiation and spatial scale effects may help to explain the maintenance of high species richness in sub-alpine meadow communities.

Effects of positive interactions, size symmetry of competition and abiotic stress on self-thinning in simulated plant populations.

BACKGROUND AND AIMS: Competition drives self-thinning (density-dependent mortality) in crowded plant populations. Facilitative interactions have been shown to affect many processes in plant populations and communities, but their effects on self-thinning trajectories have not been investigated. METHODS: Using an individual-based 'zone-of-influence' model, we studied the potential effects of the size symmetry of competition, abiotic stress and facilitation on self-thinning trajectories in plant monocultures. In the model, abiotic stress reduced the growth of all individuals and facilitation ameliorated the effects of stress on interacting individuals. KEY RESULTS: Abiotic stress made the log biomass-log density relationship during self-thinning steeper, but this effect was reduced by positive interactions among individuals. Size-asymmetric competition also influenced the self-thinning slope. CONCLUSIONS: Although competition drives self-thinning, its course can be affected by abiotic stress, facilitation and competitive symmetry.

Competitive regulation of plant allometry and a generalized model for the plant self-thinning process.

Taking into account the individual growth form (allometry) in a plant population and the effects of intraspecific competition on allometry under the population self-thinning condition, and adopting Ogawa's allometric equation 1/y = 1/axb + 1/c as the expression of complex allometry, the generalized model describing the change mode of r (the self-thinning exponential in the self-thinning equation, log M = K + log N, where M is mean plant mass, K is constant, and N is population density) was constructed. Meanwhile, with reference to the changing process of population density to survival curve type B, the exponential, r, was calculated using the software MATHEMATICA 4.0. The results of the numerical simulation show that (1) the value of the self-thinning exponential, r, is mainly determined by allometric parameters; it is most sensitive to change of b of the three allometric parameters, and a and c take second place; (2) the exponential, r, changes continuously from about -3 to the asymptote -1; the slope of -3/2 is a transient value in the population self-thinning process; (3) it is not a 'law' that the slope of the self-thinning trajectory equals or approaches -3/2, and the long-running dispute in ecological research over whether or not the exponential, r, equals -3/2 is meaningless. So future studies on the plant self-thinning process should focus on investigating how plant neighbor competition affects the phenotypic plasticity of plant individuals, what the relationship between the allometry mode and the self-thinning trajectory of plant population is and, in the light of evolution, how plants have adapted to competition pressure by plastic individual growth.