Temporary effect of postharvest UV-C irradiation on gene expression profile in tomato fruit

To obtain an overall view on gene expression during the early stage (24 h) of tomato fruit in response to postharvest UV-C irradiation (4 kJ/m(2)), we performed a microarray analysis by using Affymetrix Tomato Genechip. The results showed that 274 and 403 genes were up- or down-regulated, respectively, more than two folds in postharvest tomato fruit irradiated with UV-C as compared with that in control fruit. The up-regulated genes mainly involve in signal transduction, defense response and metabolism. Conversely, genes related to cell wall disassembly, photosynthesis and lipid metabolism were generally down-regulated. These results opened ways to probe into the molecular mechanisms of the effects of postharvest UV-C irradiation on increased disease resistance, delayed softening, better quality maintenance and prolonged postharvest life in tomato fruit.     

Strong inhibition of estrone-3-sulfatase activity by pregnenolone 16alpha-carbonitrile but not by several analogs lacking a 16alpha-nitrile group

In recent years, development of potent inhibitors for estrogen sulfatases has become an actively pursued strategy for chemoprevention and/or chemotherapy of estrogen-dependent human breast cancers. We report here our findings that pregnenolone 16alpha-carbonitrile (PCN) is a potent inhibitor of estrone-3-sulfatase activity of rats and also humans. PCN inhibited in a concentration-dependent manner the desulfation of estrone-3-sulfate catalyzed by liver microsomal and nuclear fractions of female Sprague-Dawley rats. The inhibition of estrone-3-sulfatase activity in these two subcellular fractions showed a biphasic pattern, with a highly sensitive phase seen at 78 nM to 1.25 microm of PCN followed by a markedly less-sensitive phase at > 2.5 microm of PCN. Interestingly, several of PCN's structural analogs without a 16alpha-nitrile group showed little or no inhibitory effect on rat liver microsomal E(1)-3-sulfatase activity. Double-reciprocal analysis showed that the inhibition of rat liver microsomal E(1)-3-sulfatase activity by PCN was essentially competitive in nature. When microsomes from six human term placentas were tested for their E(1)-3-sulfatase activity, PCN showed a similar biphasic inhibition of placental E(1)-3-sulfatase. Likewise, several of its structural analogs showed little or no inhibitory effect on placental E(1)-3-sulfatase activity. Computational analysis of the D-ring structure of PCN and other structurally similar analogs used in the study suggests that the potent sulfatase-inhibiting activity of PCN may be partly due to its unique steric orientation and size of the 16alpha-nitrile group. This knowledge may be useful for the rational design of more potent steroidal inhibitors of E(1)-3-sulfatase by introducing an additional nitrile group to their C16alpha-position.     

Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice

Mucin-type core 1-derived O-glycans, one of the major types of O-glycans, are highly expressed in mammary gland epithelium. Abnormal O-glycans such as Tn antigen are found in over 90% of breast cancers; however, the in vivo role of these aberrant O-glycans in the etiology of breast cancer is unclear. We generated mice with mammary epithelial specific deletion of core 1-derived O-glycans. By crossing with two spontaneous mouse breast cancer models, we determined that loss of core 1-derived O-glycans delays the onset and progression of breast cancer development. Deficiency of core 1 O-glycosylation impaired the localization of Muc1, a major O-glycoprotein, on the apical surfaces of mammary epithelium. Signaling mediated by Muc1, which is critical for breast cancer development, was also defective in the absence of core 1 O-glycans. This study reveals an unexpected role of core 1-derived O-glycans in breast cancer development in mice.     

Nonlocal Immunized Mid-Infrared Magnetic Hot Spots in Graphene Junctions

Magnetic hot spots, which implies confinements and enhancements of magnetic fields, are demonstrated in graphene junctions (GJs) in the mid-infrared range. The appearance of magnetic hot spots in GJs comes from the conduction currents in the junction. In further, the extinction resonance peaks suffer blue shift, along with the increases in the magnetic fields inside junction area, when the junction width reduces. In opposite to the circumstances for electric field enhancements, neither magnetic field enhancements nor resonance frequency of GJs is perturbed by the intrinsic nonlocal electronic response of graphene. Such nonlocality immunized magnetic enhancement could be explained by the polarization dependent property of nonlocal effect.     

Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway

Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the autophagy regulation machinery has been widely studied, the key epigenetic control of autophagy process still remains unknown. Here we report that the methyltransferase EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) epigenetically represses several negative regulators of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, such as TSC2, RHOA, DEPTOR, FKBP11, RGS16 and GPI. EZH2 was recruited to these genes promoters via MTA2 (metastasis associated 1 family, member 2), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA2 was identified as a new chromatin binding protein whose association with chromatin facilitated the subsequent recruitment of EZH2 to silenced targeted genes, especially TSC2. Downregulation of TSC2 (tuberous sclerosis 2) by EZH2 elicited MTOR activation, which in turn modulated subsequent MTOR pathway-related events, including inhibition of autophagy. In human colorectal carcinoma (CRC) tissues, the expression of MTA2 and EZH2 correlated negatively with expression of TSC2, which reveals a novel link among epigenetic regulation, the MTOR pathway, autophagy induction, and tumorigenesis.     

Prolactin increases tumor necrosis factor alpha expression in peripheral CD14 monocytes of patients with rheumatoid arthritis

Tumor necrosis factor (TNF)-α is one of the major proinflammatory mediators of rheumatic arthritis (RA); the regulatory factors for TNF-α release is not fully understood. This study aims to investigate the role of prolactin receptor (PRLR) activation in regulating the expression and release of TNF-α from CD14⁺ monocytes. The results showed that the expression of PRLR was detectable in CD14⁺ monocytes of healthy subjects, which was markedly increased in RA patients. Exposure to PRL in the culture increased the expression and release of TNF-α from CD14⁺ monocytes, which was abolished by the PRLR gene silencing or blocking the mitogen activated protein (MAPK) pathway. We conclude that exposure to PRL increases TNF-α release from CD14⁺ monocytes of RA patients, which can be abolished by PRLR gene silencing or treating with MAPK inhibitor.     

RBS1, an RNA Binding Protein,Interacts with SPIN1 and Is Involved in Flowering Time Control in Rice

The rice U-box/ARM E3 ubiquitin ligase SPL11 negatively regulates programmed cell death (PCD) and disease resistance, and controls flowering time through interacting with the novel RNA/DNA binding KH domain protein SPIN1. Overexpression of Spin1 causes late flowering in transgenic rice under short-day (SD) and long-day (LD) conditions. In this study, we characterized the function of the RNA-binding and SPIN1-interacting 1 (RBS1) protein in flowering time regulation. Rbs1was identified in a yeast-two-hybrid screen using the full-length Spin1 cDNA as a bait and encodes an RNA binding protein with three RNA recognition motifs. The protein binds RNA in vitro and interacts with SPIN1 in the nucleus. Rbs1 overexpression causes delayed flowering under SD and LD conditions in rice. Expression analyses of flowering marker genes show that Rbs1 overexpression represses the expression of Hd3a under SD and LD conditions. Rbs1 is upregulated in both Spin1 overexpression plants and in the spl11 mutant. Interestingly, Spin1 expression is increased but Spl11 expression is repressed in the Rbs1 overexpression plants. Western blot analysis revealed that the SPIN1 protein level is increased in the Rbs1 overexpression plants and that the RBS1 protein level is also up-regulated in the Spin1 overexpression plants. These results suggest that RBS1 is a new negative regulator of flowering time that itself is positively regulated by SPIN1 but negatively regulated by SPL11 in rice.