Interplay between regulation of promoter proximal pausing, BRCA1 and PARP inhibitor, and their effects on G-MiDS

Previously in the lab we found that RNA Pol II persists around TSS region and blocks replication progression throughout S phase, it subsequently leads to under-replication of TSS region. It has been shown that cells complete duplication of this region using G2/M DNA synthesis after RNA Pol II removal. Promoter proximal pausing is a key step to regulate transcription, and it is regulated by DSIF and NELF complexes. By modulating factors (SUPT5H and NELF-A) involved in regulating promoter proximal pausing, we can control the removal of RNA Pol II from TSS region and alter the level of G2/M DNA synthesis. Additionally, PARPi has been shown to increase mitotic DNA synthesis, and NELF is a known target for PARPi. Here we show that PARPi can also increase G2/M DNA synthesis. Our studies in U2OS cells showed that depletion of SUPT5H and NELF-A leads to no difference in PARPi sensitivity comparing to control cells but failed to rescue PARPi hypersensitivity in BRCA1 knockdown cells. Importantly, we discovered functional links between BRCA1 and BRCA2 with PPP factors. Knockdown of SUPT5H, BRCA1 and BRCA2 exhibit similar pattern of transcriptional defects, and co-depletion of either SUPT5H or NELF-A with BRCA1 can induce synthetic lethality. This may have an impact on the survival/relapse of BRCA1/BRCA2 mutated patients, by analysing BRCA1 and BRCA2 mutant ovarian and breast cancer patients’ clinical data, we found some associations between the expression level of DSIF and NELF complex subunits and patients’ overall survival and relapse rate

Geodynamic setting of Late Cretaceous Sn–W mineralization in southeastern Yunnan and northeastern Vietnam

The Sn–W mineralization in SE Yunnan Province, China and NE Vietnam shares many similarities. Through comparing the geological and geochronological data, we suggest the Sn–W deposits and the associate igneous rocks in the region represent one regional magmatic-mineralization event. To explore the geodynamic setting of these mineralization and magmatic activities, a geochronological dataset in the regions has been presented, containing data of this study and previously published. The dataset shows that the Late Cretaceous magmatic–mineralization–metamorphic activities widely distribute along the eastern Asian continental margin. Existing studies support that this is the product of the subduction of the Palaeo-Pacific Plate beneath the Eurasian continent, which probably formed under an Andean-type active continental margin setting. According to the exhibited data, we preliminarily conclude that the late Cretaceous magmatic and Sn–W mineralization activities in the southeast Yunnan and northeast Vietnam region is one part of this subduction activities and should have formed under the same geodynamic setting

DDX60 Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker

DDX60, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of DDX60 in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, P < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of DDX60 in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. DDX60 expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = −0.24). Furthermore, DDX60 expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like CTLA-4, PD-L1, EGF, CD96, and CD226, were all positively related with DDX60 (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, P < 0.0001) and GBM cells. These results indicated that DDX60 might have important clinical significance in glioma and could serve as a potential immune therapeutic target

Geology and Geochronology of the Miocene Rio Blanco Porphyry Cu-Mo Deposit, Northern Peru

The Rio Blanco porphyry Cu-Mo deposit occurs at the north end of the Miocene metallogenic belt of northern Peru. It has a thick supergene enrichment blanket; while normal for hyperarid Chile, this is unusual in mountainous, cloud forest terrain. Rio Blanco is hosted by the Portachuela batholith. Zircon U-Pb dating shows that the youngest part of the batholith was emplaced at 12.43 ± 0.13 Ma. The deposit formed during three magmatic-hydrothermal cycles. Cycle 1, by far the most important, occurred at 11.50 ± 0.17 to 10.92 ± 0.14 Ma (zircon U-Pb). Two intermineralization intrusions caused early potassic and propylitic alteration. This was then overprinted by a blanket of quartz-sericite, grading down into sericite-chlorite alteration. Cycle 1 was finally cut by a quartz-sericite–cemented breccia, which contains the highest-grade hypogene Cu-Mo grades. A cycle 1 molybdenite-bearing vein has a molybdenite Re-Os model age of 11.43 ± 0.16 Ma. Molybdenite Re-Os dating of the quartz-sericite–cemented breccias shows brecciation occurred at 11.28 ± 0.24 to 11.11 ± 0.18 Ma. Cycle 2 was restricted to the east side, where narrow porphyritic dacite 1 dikes (dated by zircon U-Pb at 10.62 ± 0.16 Ma) show biotite alteration and economic copper. Cycle 3, at 10.02 ± 0.12 to 9.06 ± 0.09 Ma (zircon U-Pb), was triggered by a swarm of NE-striking quartz-plagioclase porphyry and porphyritic dacite 2 dikes. Alteration was milder, and this cycle did not introduce economic copper. Nonmineralized pebble dikes cut the system, emanating from a major diatreme, about 3 × 1.3 km in size, on the north side of the deposit. The magmatic-hydrothermal history spanned about 2.5 m.y., with economic mineralization over about 1.48 m.y. However, metals were mostly introduced during cycle 1, which lasted approximately 0.58 m.y. Our work shows that while multiple magmatic-hydrothermal cycles produced Rio Blanco, sufficient metals were introduced to form a giant porphyry deposit within a single magmatic-hydrothermal cycle

A new metallogenical association (Sn-Cd-In-Zn-Ag-Au) in the Deseado auroargentiferous province, Deseado Massif, Patagonia, Argentina

A new metallogenical association (Sn-Cd-In-Zn-Ag-Au) is reported for the low sulphidation epithermal Deseado Auroargentiferous Province, in Patagonia, Argentina. The anomalous presence of Sn, Cd and In, together with anomalies of Zn and Ag, and also high contents of Cu, Mn, Pb, W and Bi in a complex sulphur-rich mineralogy, represent a new metallogenical association. This assemblage could be related to a higher temperature mineralization or a different type into the epithermal range. The presence of this new metallogenical association increases the mining potential of the region, extending exploration targets in this metallogenical province and must be considered during future exploration duties in the region.Instituto de Recursos Minerale

Internet Recruitment of Asian American Breast Cancer Survivors

The purpose of this paper is to identify practical issues in Internet recruitment of racial/ethnic minorities by analyzing an Internet intervention study conducted with Asian American breast cancer survivors, and to propose directions for recruitment of racial/ethnic minorities for future Internet research. Six practical issues were identified: (a) a relatively fewer number of Internet communities/groups; (b) hindrances in establishing authenticity; (c) difficulties in gaining entrée from the webmasters or website owners of Internet communities/groups; (d) the necessity of racially/ethnically matched research team members; (e) flexibility required in recruitment strategies; and (f) strategies to overcome the low response rate

A proposed disease classification system for duck viral hepatitis

The nomenclature of duck viral hepatitis (DVH) was historically not a problem. However, 14 hepatotropic viruses among 10 different genera are associated with the same disease name, DVH. Therefore, the disease name increasingly lacks clarity and may no longer fit the scientific description of the disease. Because one disease should not be attributed to 10 genera of viruses, this almost certainly causes misunderstanding regarding the disease-virus relationship. Herein, we revisited the problem and proposed an update to DVH disease classification. This classification is based on the nomenclature of human viral hepatitis and the key principle of Koch's postulates (“one microbe and one disease”). In total, 10 types of disease names have been proposed. These names were literately matched with hepatitis-related viruses. We envision that this intuitive nomenclature system will facilitate scientific communication and consistent interpretation in this field, especially in the Asian veterinary community, where these diseases are most commonly reported