Gravity profoundly influences plant growth and development. Plants respond to changes in orientation by using gravitropic responses to modify their growth. Cholodny and Went hypothesized over 80 years ago that plants bend in response to a gravity stimulus by generating a lateral gradient of a growth regulator at an organ's apex, later found to be auxin. Auxin regulates root growth by targeting Aux/IAA repressor proteins for degradation. We used an Aux/IAAbased reporter, domain II (DII)-VENUS, in conjunction with a mathematical model to quantify auxin redistribution following a gravity stimulus. Our multidisciplinary approach revealed that auxin is rapidly redistributed to the lower side of the root within minutes of a 908 gravity stimulus. Unexpectedly, auxin asymmetry was rapidly lost as bending root tips reached an angle of 408 to the horizontal. We hypothesize roots use a "tipping point" mechanism that operates to reverse the asymmetric auxin flow at the midpoint of root bending. These mechanistic insights illustrate the scientific value of developing quantitative reporters such as DII-VENUS in conjunction with parameterized mathematical models to provide high-resolution kinetics of hormone redistribution.environmental sensing | systems biology R oot gravitropism has fascinated researchers since Knight (1) and Darwin (2). More recently, reorientation of Arabidopsis seedlings has been shown to trigger the asymmetric release of the growth regulator auxin from gravity-sensing columella cells at the root apex (Fig. 1A) (3-5). The resulting lateral auxin gradient is hypothesized to drive a differential growth response, where cell expansion on the lower side of the elongation zone is reduced relative to the upper side, causing the root to bend downward (6-8). Despite representing one of the oldest hypotheses in plant biology, key questions about auxin-regulated root gravitropism remain to be experimentally determined. How rapidly does the lateral auxin gradient form? Is this timescale consistent with the theory that auxin redistribution drives root bending? How long does the lateral auxin gradient persist? What triggers auxin redistribution to return to equal levels?Our understanding of gravity-induced auxin redistribution has been limited by the tools available to monitor auxin concentrations at high spatiotemporal resolution. Currently, the most widely used tools to follow auxin distribution in tissues are auxin-inducible reporters such as DR5::GFP (3, 4). However, as an output of the auxin response pathway (Fig. 1B), the activity of the DR5 reporter does not directly relate to endogenous auxin abundance, but also depends on additional parameters including local auxin signaling capacities and rates of transcription and translation (Fig. 1B). In practice, these intermediate processes confer a time delay of ∼1.5-2 h between changes in auxin abundance and DR5 reporter activity (9, 4), making it difficult to quantify the speed and magnitude of fold changes in auxin distribution during a root gravitropic response.Auxi...

High salt is positively associated with the risk of many diseases. However, little is known about the mechanisms. Here we showed that high salt increased proinflammatory molecules, while decreased anti-inflammatory and proendocytic molecules in both human and mouse macrophages. High salt also potentiated lipopolysaccharide-induced macrophage activation and suppressed interleukin 4-induced macrophage activation. High salt induced the proinflammatory aspects by activating p38/cFos and/or Erk1/2/cFos pathways, while inhibited the anti-inflammatory and proendocytic aspects by Erk1/2/signal transducer and activator of transcription 6 pathway. Consistent with the in vitro results, high-salt diet increased proinflammatory gene expression of mouse alveolar macrophages. In mouse models of acute lung injury, high-salt diet aggravated lipopolysaccharide-induced pulmonary macrophage activation and inflammation in lungs. These results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na).

Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulated in HCC tissues and inversely correlated with miR-124 expression. The overexpression of miR-124 decreased AQP3 expression. Indeed, AQP3 overexpression promoted cell proliferation and migration, whereas miR-124 knockdown suppressed cell proliferation and migration. Furthermore, we found that circular RNA HIPK3 (circHIPK3) acted as a miR-124 sponge and regulated the expression of the miR-124 target gene AQP3. circHIPK3 was upregulated in HCC tissues and positively correlated with AQP3 expression. Thus, silencing circHIPK3 inhibited cell proliferation and migration by downregulating AQP3 expression. Moreover, miR-124 inhibition rescued circHIPK3 knockdown induced reduction in cell proliferation and migration, as well as AQP3 expression. In vivo experiments also confirmed that circHIPK3 regulated xenograft tumor growth via the miR-124-AQP3 axis. These observations indicate a possible novel therapeutic strategy involving circular RNAs in HCC.