We have measured the distance to the massive star-forming region W3OH in the Perseus spiral arm of the Milky Way to be 1.95 ± 0.04 kiloparsecs (5.86 x10¹⁶ km). This distance was determined by ...triangulation, with Earth's orbit as one segment of a triangle, using the Very Long Baseline Array. This resolves the long-standing problem that there is a discrepancy of a factor of 2 between different techniques used to determine distances. The reason for the discrepancy is that this portion of the Perseus arm has anomalous motions. The orientation of the anomalous motion agrees with spiral density-wave theory, but the magnitude of the motion is somewhat larger than most models predict.
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease of temporomandibular joint, which has a high incidence and affects the quality of patients' life. While the pathogenesis of ...TMJOA remains unclear. It has been found that angiogenesis is involved in the development of TMJOA and it is closely related to the degradation of articular cartilage matrix, subchondral ossification, osteophyte formation and pain. This article reviews the recent advances in the study of angiogenesis in TMJOA, and provides a prospect for the treatment of TMJOA.
ATP -competitive mTO R kinase inhibitors (mTorKIs) are a new generation of mTO R-targeted agents with more potent anticancer activity than rapamycin in several tumor models. However, the sensitivity ...and resistance of cancer cells to mTorKIs remain poorly understood. In this study, we tested mTorKIs against a large panel of colorectal cancer (CRC) cell lines, and found that mTorKIs displayed broader anti-CRC activity than rapamycin, including CRC cells with K-Ras or B-Raf mutations, suggesting that these mTorKIs are particularly useful for CRCs resistant to EGFR inhibitors. Unexpectedly, we found that 40% CRC cell lines were intrinsically drug resistant. Moreover, we discovered an mTO R-independent 4E- BP1 phosphorylation that was correlated with mTorKI resistance. Altogether, our findings provide compelling preclinical support for testing mTorKIs in human CRC clinical trials. They further reveal the existence of significant intrinsic mTorKI drug resistance in cancer cells and suggest that 4E-BP1 phosphorylation is a predictive biomarker for mTorKI sensitivity and resistance.
ABSTRACT We conducted Very Large Array C-configuration observations to measure positions and luminosities of Galactic Class II 6.7 GHz methanol masers and their associated ultra-compact H ii regions. ...The spectral resolution was 3.90625 kHz and the continuum sensitivity reached 45 Jy beam−1. We mapped 372 methanol masers with peak flux densities of more than 2 Jy selected from the literature. Absolute positions have nominal uncertainties of 0 3. In this first paper on the data analysis, we present three catalogs; the first gives information on the strongest feature of 367 methanol maser sources, and the second provides information on all detected maser spots. The third catalog presents derived data of the 127 radio continuum counterparts associated with maser sources. Our detection rate of radio continuum counterparts toward methanol masers is approximately one-third. Our catalogs list properties including distance, flux density, luminosity, and the distribution in the Galactic plane. We found no significant relationship between luminosities of masers and their associated radio continuum counterparts, however, the detection rate of radio continuum emission toward maser sources increases statistically with the maser luminosities.
SOX9 encodes a transcription factor that governs cell fate specification throughout development and tissue homeostasis. Elevated SOX9 is implicated in the genesis and progression of human tumors by ...increasing cell proliferation and epithelial-mesenchymal transition. We found that in response to UV irradiation or genotoxic chemotherapeutics, SOX9 is actively degraded in various cancer types and in normal epithelial cells, through a pathway independent of p53, ATM, ATR and DNA-PK. SOX9 is phosphorylated by GSK3β, facilitating the binding of SOX9 to the F-box protein FBW7α, an E3 ligase that functions in the DNA damage response pathway. The binding of FBW7α to the SOX9 K2 domain at T236-T240 targets SOX9 for subsequent ubiquitination and proteasomal destruction. Exogenous overexpression of SOX9 after genotoxic stress increases cell survival. Our findings reveal a novel regulatory mechanism for SOX9 stability and uncover a unique function of SOX9 in the cellular response to DNA damage. This new mechanism underlying a FBW7-SOX9 axis in cancer could have implications in therapy resistance.
MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their ...clinical significance for hepatocellular carcinoma.
Patients with hepatocellular carcinoma, undergoing hepatectomy were randomly divided into training set (60 patients) and test set (50 patients). Other 56 patients were used as an independent cohort. The miRNA expression levels were detected by microarray and verified by quantitative real-time reverse transcription-PCR (qRT-PCR).
A 30-miRNA signature consisting of 10 downregulated and 20 upregulated miRNAs was established for distinguishing hepatocellular carcinoma from noncancerous liver tissues in the training set with 99.2% accuracy. The classification accuracies of this signature were 97% and 90% in the test set and independent cohort, respectively. The expression level of four miRNAs in the 30-miRNA signature was verified by qRT-PCR in the training set. Twenty miRNAs were then selected to construct prognostic signature in the training set. Of the 20 miRNAs, six were risk factors and 14 were protective factors. A formula based on the 20 miRNAs was built to compute prognostic index. Kaplan-Meier analysis showed that patients with a higher prognostic index had a significantly lower survival than those with a low index. This was verified in the test and independent sets. Multivariate analysis indicated that the 20-miRNA signature was an independent prognostic predictor.
The 30- and 20-miRNA signatures identified in this study should provide new molecular approaches for diagnosis and prognosis of patients with hepatocellular carcinoma and clues for elucidating molecular mechanism of hepatocarcinogenesis.
In this study, we present a sequential electrochemical process for integral treatment of anaerobic sludge, combining for the first time electrochemical peroxidation (ECP) and electro-Fenton (EF). In ...the first step, ECP (consisting of H2O2-assisted electrocoagulation with Fe electrodes) was applied as a conditioning and stabilizing method, whose synergistic electrocoagulation/Fenton oxidation effects considerably reduced the COD, TOC and total suspended solids (TSS) by 89.3%, 75.4% and 85.6%, respectively, under optimized conditions (initial pH of 5, H2O2/Fe2+ dose ratio of 5, 15.38 mA cm−2 and 2 h treatment). Furthermore, total coliforms were completely killed within the first hour of treatment. In the second step, EF was successfully applied to mineralize the remaining organic fraction in the liquid effluent after dewatering, achieving 91.6% and 87.2% of COD and TOC removal, respectively, after 4 h of treatment under optimal conditions (pH 3 and 25 mA cm−2), while almost total COD and TOC removal was attained in 8 h. The Fe sludge generated at the end of the ECP treatment was easily dewatered by filtration and 20.9 g of nutrient-rich dry sludge were produced. The overall cost of the ECP-EF treatment was S$ 0.05 L-1 sludge. The combined effects of coagulation and Fenton oxidation during ECP revealed that the treatment efficiency is strongly dependent on the rheological properties of the sludge sample.
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•Integral sludge treatment by electrochemical peroxidation (ECP) - electro-Fenton (EF).•89.3% COD, 75.4% TOC, 85.6% TSS and complete coliform removal yields after 2 h of ECP.•Near complete COD and TOC removal after 2 h of ECP and 8 h of EF.•54.75 g L−1 of dry sludge produced suitable for land application.•Treatment efficiency strongly dependent on sludge rheological properties.
We have found earlier that Tor1 binds to 5S rDNA chromatin but the functional significance has not been established. Here, we show that association with 5S rDNA chromatin is necessary for TOR complex ...1 (TORC1) to regulate the synthesis of 5S ribosomal RNA and transfer RNAs (tRNAs) by RNA polymerase (Pol) III, as well as the phosphorylation and binding to Pol III‐transcribed genes of the Pol III repressor Maf1. Interestingly, TORC1 does not bind to tRNA genes, suggesting that TORC1 modulates tRNA synthesis indirectly through Maf1 phosphorylation at the rDNA loci. We also find that Maf1 cytoplasmic localization is dependent on the SSD1‐v allele. In W303 cells that carry the SSD1‐d allele, Maf1 is constitutively nuclear but its nucleolar localization is inhibited by TORC1, indicating that TORC1 regulates nucleoplasm‐to‐nucleolus transport of Maf1. Finally, we show that TORC1 interacts with Maf1 in vivo and phosphorylates Maf1 in vitro, and regulates Maf1 nucleoplasm‐to‐nucleolus translocation. Together, these observations provide new insights into the chromatin‐dependent mechanism by which TORC1 controls transcription by Pol III.
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