Planck Galactic Cold Clumps at High Galactic Latitude-a Study with CO Lines

Gas at high Galactic latitude is a relatively little noticed component of the interstellar medium. In an effort to address this, 41 Planck Galactic Cold Clumps at high Galactic latitude (HGal; divide b divide > 25 degrees) were observed in (CO)-C-12, (CO)-C-13, and (CO)-O-18 J = 1-0 lines, using the Purple Mountain Observatory 13.7 m telescope. (CO)-C-12 (1-0) and (CO)-C-13 (1-0) emission was detected in all clumps, while (CO)-O-18 (1-0) emission was only seen in 16 clumps. The highest and average latitudes are 71.degrees 4 and 37.degrees 8, respectively. Fifty-one velocity components were obtained, and then each was identified as a single clump. Thirty-three clumps were further mapped at 1 ' resolution, and 54 dense cores were extracted. Among dense cores, the average excitation temperature T (ex) of (CO)-C-12 is 10.3 K. The average line widths of thermal and nonthermal velocity dispersions are 0.19 and 0.46 km s(-1), respectively, suggesting that these cores are dominated by turbulence. Distances of the HGal clumps given by Gaia dust reddening are about 120-360 pc. The ratio of X (13)/X (18) is significantly higher than that in the solar neighborhood, implying that HGal gas has a different star formation history compared to the gas in the Galactic disk. HGal cores with sizes from 0.01 to 0.1 pc show no notable Larson's relation, and the turbulence remains supersonic down to a scale of slightly below 0.1 pc. None of the HGal cores that bear masses from 0.01 to 1 M (circle dot) are gravitationally bound, and all appear to be confined by outer pressure.Peer reviewe

PLANCK COLD CLUMPS IN THE lambda ORIONIS COMPLEX. I. DISCOVERY OF AN EXTREMELY YOUNG CLASS 0 PROTOSTELLAR OBJECT AND A PROTO-BROWN DWARF CANDIDATE IN THE BRIGHT-RIMMED CLUMP PGCC G192.32-11.88

We are performing a series of observations with ground-based telescopes toward Planck Galactic cold clumps (PGCCs) in the lambda Orionis complex in order to systematically investigate the effects of stellar feedback. In the particular case of PGCC G192.32-11.88, we discovered an extremely young Class 0 protostellar object (G192N) and a proto-brown dwarf candidate (G192S). G192N and G192S are located in a gravitationally bound brightrimmed clump. The velocity and temperature gradients seen in line emission of CO isotopologues indicate that PGCC G192.32-11.88 is externally heated and compressed. G192N probably has the lowest bolometric luminosity (similar to 0.8 L-circle dot) and accretion rate (6.3 x 10(-7) M-circle dot yr(-1)) when compared with other young Class 0 sources (e.g., PACS Bright Red Sources) in the Orion complex. It has slightly larger internal luminosity (0.21 +/- 0.01 L-circle dot) and outflow velocity (similar to 14 km s(-1)) than the predictions of first hydrostatic cores (FHSCs). G192N might be among the youngest Class 0 sources, which are slightly more evolved than an FHSC. Considering its low internal luminosity (0.08 +/- 0.01 L-circle dot) and accretion rate (2.8 x 10(-8) M-circle dot yr(-1)), G192S is an ideal proto-brown dwarf candidate. The star formation efficiency (similar to 0.3%-0.4%) and core formation efficiency (similar to 1%) in PGCC G192.32-11.88 are significantly smaller than in other giant molecular clouds or filaments, indicating that the star formation therein is greatly suppressed owing to stellar feedback.Peer reviewe

Epigenetic regulation of integrin-linked kinase expression depending on adhesion of gastric carcinoma cells

Cell adhesion to the extracellular matrix (ECM) regulates gene expressions in diverse dynamic environments. However, the manner in which gene expressions are regulated by extracellular cues is largely unknown. In this study, suspended gastric carcinoma cells showed higher basal and transforming growth factor- 1 (TGF 1)-mediated acetylations of histone 3 (H3) and Lys9 of H3 and levels of integrinlinked kinase (ILK) mRNA and protein than did fibronectin-adherent cells did. Moreover, the insignificant acetylation and ILK expression in adherent cells were recovered by alterations of integrin signaling and actin organization, indicating a connection between cytoplasmic and nuclear changes. Higher acetylations in suspended cells were correlated with associations between Smad4, p300/CBP, and Lys9-acetylated H3. Meanwhile, adherent cells showed more associations between HDAC3, Ski, and MeCP2. Chromatin immunoprecipitations with anti-acetylated H3, Lys9-acetylated H3, or p300/CBP antibody resulted in more coprecipitated ILK promoter, correlated with enhanced ILK mRNA and protein levels, in suspended cells. Moreover, ILK expression inversely regulated cell adhesion to ECM proteins, and its overexpression enhanced cell growth in soft agar. These observations indicate that cell adhesion and/or its related molecular basis regulate epigenetic mechanisms leading to a loss of ILK transcription, which in turn regulates cell adhesion property in a feedback linkage

Integrin Signaling and Cell Spreading Mediated by Phorbol 12-Myristate 13-Acetate Treatment

Spreading of SNU16mAd gastric carcinoma cells was previously shown to be regulated via a signaling network from transforming growth factor b1 (TGFb1) to integrins signaling, through a mediation of protein kinase Cd(PKCd). However, in the previous study, the roles of PKCd appeared complicated. In this study to clarify the roles of PKCd in the spreading of the gastric carcinoma cells, we questioned if PKC activation via phorbol 12-myristate 13-acetate (PMA) treatment could mimic the TGFb1 effects. An acute PMA treatment increased phosphorylations of focal adhesion (FA) kinase, paxillin, c-Src, and cofilin, just as TGFb1 did. Furthermore, cell spreading mediated by TGFb1- or acute PMA treatment correlated with activation of RhoA, which regulates actin reorganization and FA formation. However, stress fiber formation was prominent in TGFb1-treated cells, compared to cortical actin organization in PMA-treated cells. Altogether, these observations indicate that acute PMA treatment could mimic the TGFb1 mechanisms for cell spreading through subtly different effects on actin reorganization.Grant sponsor: Korea Research Foundation Grant; Grant number: KRF-2004-015-C00445

Cooperation between integrin alpha5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity

Tetraspan TM4SF5 is highly expressed in a diverse number of tumor types. Here we explore the mechanistic roles of TM4SF5 in angiogenesis. We found that TM4SF5 overexpression correlates with vascular endothelial growth factor (VEGF) expression in SNU449 hepatocytes and with vessel formation in clinical hepatocarcinoma samples. Conditioned media from TM4SF5-expressing cells enhanced viability and tube formation of primary human umbilical vein endothelial cells, and outgrowth of endothelial cells from aorta ring segments, which was abolished by treatment with an anti-VEGF antibody. TM4SF5 retained integrin alpha(5) on the cell surface for VEGF induction, and preincubation with anti-integrin alpha(5) antibody abolished TM4SF5-mediated VEGF expression and secretion. TM4SF5-mediated effects required integrin alpha(5), c-Src, and signal transducer and activator of transcription 3 (STAT3). In addition, tumors from nude mice injected with TM4SF5-expressing cells and from clinical human hepatocarcinoma tissues showed enhanced integrin alpha(5) expression, vessel formation, and signaling activity, which were inhibited by administration of anti-integrin alpha(5) or -VEGF antibody. This study suggests that TM4SF5 facilitates angiogenesis of neighboring endothelial cells through VEGF induction, mediated by cooperation between TM4SF5 and integrin alpha(5) of epithelial cells

Feasibility of ovarian preservation in patients with early stage endometrial carcinoma

OBJECTIVES: Our objective was to determine the frequency of a coexisting ovarian malignancy and to evaluate the feasibility of ovarian preservation in patients with early stage endometrial carcinoma. METHODS: Endometrial cancer patients who received primary surgical treatment between 1992 and 2004 were identified using the institution's tumor registry. Information regarding patient age, preoperative and intraoperative evaluations, pathologic reports, and follow-up results was abstracted from medical records. RESULTS: Coexisting ovarian malignancy was detected in 19 (7.31%) of 260 patients who underwent surgical treatment (12 metastatic and 7 synchronous primaries). The independent risk factors of a coexisting ovarian malignancy, as determined using a logistic regression model, were intraoperative extrauterine disease, non-endometrioid histology, lymph node metastasis, and patient age, and the presence of intraoperative extrauterine disease was found to most significantly predict ovarian involvement (OR=542.1; 95% CI, 57.18 to 5139.23). Seventeen of the 19 cases showed abnormal intraoperative gross findings around adnexa or other sites. Among the 206 patients without any evidence of intraoperative extrauterine disease, the coexisting ovarian malignancy rate was 0.97% (2/206), and zero for those under age of 45. In 35 patients, grossly normal ovaries were selectively saved, and no recurrence or cancer-related death occurred (median duration of follow-up: 76 months, range 3-121). CONCLUSIONS: The risk of coexisting malignancy in patients without predictable risk factors is minimal. Therefore, it is possible to preserve ovaries in young women with early stage endometrial carcinoma with a thorough preoperative evaluation and extensive intraoperative exploration

8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia

Free 8-hydroxydeoxyguanosine (oh(8)dG), a nucleoside of 8-hydroxyguanine (oh(8)Gua), present in cytosol is not incorporated into DNA. However, nothing is known about its biological function when it presents in cytosol as a free form. We demonstrate here for the first time that oh(8)dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh(8)dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1beta, IL-6, and TNF-alpha, in activated BV2 cells. We also found that oh(8)dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh(8)dG suppressed recruitment of STATs and p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken together, these results provide new aspects of oh(8)dG as an anti-inflammatory agent

Antagonistic regulation of transmembrane 4 L6 family member5 attenuates fibrotic phenotypes in CCl(4) -treated mice.

The development of liver fibrosis from chronic inflammation can involve epithelial–mesenchymal transition (EMT). Severe liver fibrosis can progress to cirrhosis, and further to hepatocellular carcinoma. Because the tetraspanin transmembrane 4 L6 family member 5 (TM4SF5) induces EMT and is highly expressed in hepatocellular carcinoma, it is of interest to investigate whether TM4SF5 expression is correlated with EMT processes during the development of fibrotic liver features. Using hepatic cells in vitro and a CCl4-mediated mouse liver in vivo model, we examined whether TM4SF5 is expressed during liver fibrosis mediated by CCl4 administration and whether treatment with anti-TM4SF5 reagent blocks the fibrotic liver features. Here, we found that TM4SF5 expression was induced by the transforming growth factor (TGF)b1 and epidermal growth factor signaling pathways in hepatocytes in vitro. In the CCl4-mediated mouse liver model, TM4SF5 was expressed during the liver fibrosis mediated by CCl4 administration and correlated with a-smooth muscle actin expression, collagen I deposition, and TGFb1 and epidermal growth factor receptor signaling activation in fibrotic septa regions. Interestingly, treatment with anti- TM4SF5 reagent blocked the TM4SF5-mediated liver fibrotic features: the formation of fibrotic septa with a-smooth muscle actin expression and collagen I deposition was attenuated by treatment with anti-TM4SF5 reagent. These results suggest that TM4SF5 expression mediated by TGFb1 and growth factor can facilitate fibrotic processes during chronic liver injuries. TM4SF5 is thus a candidate target for prevention of liver fibrosis following chronic liver injury.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000003910/1SEQ:1PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:0000003910ADJUST_YN:NEMP_ID:A078142DEPT_CD:375CITE_RATE:3.79FILENAME:65MKK-FEBSJ.pdfDEPT_NM:약학과EMAIL:[email protected]:

Cell adhesion status-dependent histone acetylation is regulated through intracellular contractility-related signaling activities

Although histone acetylation is important for epigenetic gene transcription, histone acetylation regulation by extracellular cues has rarely been evidenced. Here, we examined whether and how histone acetylation is regulated by cell adhesion-mediated signaling. Gastric carcinoma cells in suspension showed a higher histone acetylation, compared with fibronectin-adherent cells. This difference was supported by a decreased histone deacetylases activity. Furthermore, trichostatin A (TSA)-mediated histone acetylation was significantly increased only in suspended, but not in fibronectin-adherent, cells. Pharmacological inhibition of intracellular contractility-related myosin light chain kinase or RhoA-kinase (ROCK) or expression of ROCK1 small interfering RNA, dominant negative RhoA, or active Rac1 decreased basal and TSA-mediated histone H3 acetylationsin suspended cells, whereas inhibition of calmodulin-dependent protein kinase II or transient overexpression of wild type myosin light chain kinase enhanced the acetylations. Meanwhile, chromatin immunoprecipitation showed higher basal and TSA-enhanced associations of ROCK1 promoter regions with Lys(9)-acetylated histone 3 in suspended cells than in fibronectin-adherent cells and expression of ROCK1 was higher and further increased by TSA treatment in suspension. In addition, phosphorylation of myosin light chain was further increased by TSA in suspension and higher in anchorage-independent cells over adherently growing cells, indicating an inverse relationship between ROCK1 expression-mediated contractility and cell adhesion abilities. Cell adhesion analysis showed that pharmacological activation of intracellular contractility-related signaling activities decreased cell adhesion abilities, whereas inhibition of them increased the adhesion. Taken together, these observations suggest that cell adhesion-related signal transduction regulates histone acetylation, presumably through a close functional linkage between intracellular contractility and histone deacetylases activity/histone acetylation

Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells

Tumor angiogenesis is required for tumor development and is stimulated by angiogenic inducers like VEGF (vascular endothelial growth factor). Our previous study demonstrated that STAT3 (signal transducer and activator of transcription 3) up-regulates HIF-1alpha (hypoxia inducible factor-1alpha) protein stability and enhances HIF-1-mediated VEGF expression in hypoxic solid tumor cells, thus suggesting that the inhibition of STAT3 signaling may have clinical applications. In this study, we examined in vitro and in vivo, whether caffeic acid (CA) or its derivative CADPE [3-(3,4-dihydroxy-phenyl)-acrylic acid 2-(3,4-dihydroxy-phenyl)-ethyl ester] exert anticancer activity by targeting STAT3. It was found that CA or CADPE significantly inhibit STAT3 activity, and that this in turn down-regulates HIF-1alpha activity. Consequently, sequential blockade of STAT3 and HIF-1alpha resulted in the down-regulation of VEGF by inhibiting their recruitment to the VEGF promoter. In mice bearing a Caki-I carcinoma, both CA and CADPE retarded tumor growth and suppressed STAT3 phosphorylation, HIF-1alpha expression, vascularization and STAT3-inducible VEGF gene expression in tumors. Taken together, our results demonstrate that CA and CADPE are potential inhibitors of STAT3 and that they suppress tumor angiogenesis by inhibiting the activity of STAT3, the expression of HIF-1alpha and VEGF