High Glucose Induces Reactivation of Latent Kaposi’s Sarcoma-Associated Herpesvirus

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29 grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose induced production of hydrogen peroxide (H2O2), which down regulated silent information regulator 1 (SIRT1), a class-III histone deacetylase (HDAC), resulting in epigenetic transactivation of KSHV lytic genes.These results suggest that high blood glucose in diabetic patients contributes to development of KS by promoting KSHV lytic replication and infection

Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells

Cdc6, which alters chromatin ultrastructure to allow DNA replication in muscle stem cells transitioning out of quiescence, is identified as a target of the MyoD transcription factor

The dynamics of E1A in regulating networks and canonical pathways in quiescent cells

<p>Abstract</p> <p>Background</p> <p>Adenoviruses force quiescent cells to re-enter the cell cycle to replicate their DNA, and for the most part, this is accomplished after they express the E1A protein immediately after infection. In this context, E1A is believed to inactivate cellular proteins (e.g., p130) that are known to be involved in the silencing of E2F-dependent genes that are required for cell cycle entry. However, the potential perturbation of these types of genes by E1A relative to their functions in regulatory networks and canonical pathways remains poorly understood.</p> <p>Findings</p> <p>We have used DNA microarrays analyzed with Bayesian ANOVA for microarray (BAM) to assess changes in gene expression after E1A alone was introduced into quiescent cells from a regulated promoter. Approximately 2,401 genes were significantly modulated by E1A, and of these, 385 and 1033 met the criteria for generating networks and functional and canonical pathway analysis respectively, as determined by using Ingenuity Pathway Analysis software. After focusing on the highest-ranking cellular processes and regulatory networks that were responsive to E1A in quiescent cells, we observed that many of the up-regulated genes were associated with DNA replication, the cell cycle and cellular compromise. We also identified a cadre of up regulated genes with no previous connection to E1A; including genes that encode components of global DNA repair systems and DNA damage checkpoints. Among the down-regulated genes, we found that many were involved in cell signalling, cell movement, and cellular proliferation. Remarkably, a subset of these was also associated with p53-independent apoptosis, and the putative suppression of this pathway may be necessary in the viral life cycle until sufficient progeny have been produced.</p> <p>Conclusions</p> <p>These studies have identified for the first time a large number of genes that are relevant to E1A's activities in promoting quiescent cells to re-enter the cell cycle in order to create an optimum environment for adenoviral replication.</p

The GEOTRACES Intermediate Data Product 2014

The GEOTRACES Intermediate Data Product 2014 (IDP2014) is the first publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2013. It consists of two parts: (1) a compilation of digital data for more than 200 trace elements and isotopes (TEIs) as well as classical hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing a strongly inter-linked on-line atlas including more than 300 section plots and 90 animated 3D scenes. The IDP2014 covers the Atlantic, Arctic, and Indian oceans, exhibiting highest data density in the Atlantic. The TEI data in the IDP2014 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at cross-over stations. The digital data are provided in several formats, including ASCII spreadsheet, Excel spreadsheet, netCDF, and Ocean Data View collection. In addition to the actual data values the IDP2014 also contains data quality flags and 1-? data error values where available. Quality flags and error values are useful for data filtering. Metadata about data originators, analytical methods and original publications related to the data are linked to the data in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2014 data providing section plots and a new kind of animated 3D scenes. The basin-wide 3D scenes allow for viewing of data from many cruises at the same time, thereby providing quick overviews of large-scale tracer distributions. In addition, the 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of observed tracer plumes, as well as for making inferences about controlling processes

E1A Interacts with Two Opposing Transcriptional Pathways To Induce Quiescent Cells into S Phase ▿

Despite data suggesting that the adenovirus E1A protein of 243 amino acids creates an S-phase environment in quiescent cells by overcoming the nucleosomal repression of E2F-regulated genes, the precise mechanisms underlying E1A's ability in this process have not yet been defined at the biochemical level. In this study, we show by kinetic analysis that E1A, as opposed to an E1A mutant failing to bind p130, can temporally eliminate corepressor complexes consisting of p130-E2F4 and HDAC1/2-mSin3B from the promoters of E2F-regulated genes in quiescent cells. Once the complexes are removed, the di-methylation of H3K9 at these promoters becomes dramatically diminished, and this in turn allows for the acetylation of H3K9/14 and the recruitment of activating E2F family members, which is then followed by the transcriptional activity of the E2F-regulated genes. Remarkably, although an E1A mutant that can no longer bind to a histone acetyltransferase (PCAF) is as capable as wild-type E1A in eliminating corepressor complexes and methyl groups from the promoters of these genes, it cannot mediate the acetylation of H3K9/14 or induce their transcription. These findings suggest that corepressors as well as coactivators are acted upon by E1A to derepress E2F-regulated genes in quiescent cells. Thus, our results highlight for the first time a functional relationship between E1A and two transcriptional pathways of differing functions for transitioning cells out of quiescence and into S phase

Experimental Study on the Creep Characteristics of Coal Measures Sandstone under Seepage Action

The seepage action of underground water accelerates the deformation of roadway surrounding rock in deep mines. Therefore, the study of creep characteristics of surrounding rock under seepage action is the basis for the stability control of roadway surrounding rock in deep water-rich areas. In this paper, a seepage-creep coupling test system for complete rock samples was established. Combined with a scanning electron microscopy (SEM) test system, the seepage-creep law of coal measures sandstone and the damage mechanism were revealed. The study results showed that the maximum creep deformation of sandstone under natural and saturation state decreased gradually with the increase of confining pressure, and the maximum creep deformation under saturation state was greater than the corresponding value under natural state when the confining pressure was same. When the confining pressure was constant, the creep deformation, the constant creep deformation rate and the accelerated creep deformation rate of sandstone increased rapidly with the increase of infiltration pressure. With the change of time, the change of permeability parameters went through three cycles; each cycle was divided into two stages, slow change stage and rapid change stage, and the rate of variation increased with the increase of the seepage pressure. Based on the macroscopic and microscopic characteristics of sandstone rupture, the connection between macroscopic and microscopic mechanism on sandstone rupture was established. The results in this paper can provide a theoretical basis for stability control of roadway surrounding rock in water-rich areas

The Municipal Sewage Discharge May Impact the Dissemination of Antibiotic-Resistant Escherichia coli in an Urban Coastal Beach

To determine the potential of the recreational marine environment as a dissemination vector of antibiotic-resistant microorganisms, the dissemination of antibiotic-resistant E. coli strains isolated from an urban coastal beach was studied. Sixty-nine and thirteen E. coli strains were isolated from the seawater and sand, respectively, in Fujiazhuang bathing beach, China. The average Antibacterial Resistance Index (ARI) value detected in the seawater is approximately three times that in beach sand. All the isolates from the sand were grouped into one cluster and only the isolates from the municipal sewage outlet were classified into three antibiogram clusters that were observed in the hetero-sites of the E. coli isolates. The E. coli strains with multiple antibiotic resistance (58% of total) were prevalent in the seawater, whereas the isolates from the sand were not detected with multiple antibiotic resistance. A significant association (p &lt; 0.05) between all phenotypic and relative genotypic resistance profiles was observed in the isolates, except in the quinolones resistance genotype. The presence of a class 1 integron was significantly correlated with the resistance of E. coli to sulfonamides, streptomycin, and levofloxacin (p &lt; 0.01). This study revealed that the municipal sewage discharge may impact the dissemination of antibiotic-resistant strains in the urban coastal beach, and that the class 1 integrons play an important role in mediating the resistance of E. coli to sulfonamide antibiotics

Controlled defect creation and removal in graphene and MoS2 monolayers

It is known that defects strongly influence the properties of two-dimensional (2D) materials. The controlled creation and removal of defects can be utilized to tailor the optical and electronic responses of these 2D materials for optoelectronic and nanoelectronic applications. In this study, we developed an efficient approach to reversibly control the defect states in mechanically exfoliated graphene and molybdenum disulfide (MoS2) monolayers. The defects were created by aluminium oxide (Al2O3) plasmas and removed by moderate thermal annealing at up to 300 °C. We employed Raman and photoluminescence (PL) as well as electrical characterization to monitor the variation of the defect level in graphene and MoS2. For graphene, Raman spectra indicate that the Al2O3 plasma induced sp3-type defects with a controlled concentration, which have been substantially removed after thermal annealing. A similar trend was also observed in monolayer MoS2, as revealed by the defect-related emission peak (Xb) in the PL spectra. We further showed that the defects induced by the Al2O3 plasma in both 2D materials can be restored to any intended level via annealing under well-controlled conditions. Our work presents a new route to the functional design of the optical and electronic properties of graphene and MoS2-based devices through defect engineering

The Response of microRNAs to Solar UVR in Skin-Resident Melanocytes Differs between Melanoma Patients and Healthy Persons

<div><p>The conversion of melanocytes into cutaneous melanoma is largely dictated by the effects of solar ultraviolet radiation (UVR). Yet to be described, however, is exactly how these cells are affected by intense solar UVR while residing in their natural microenvironment, and whether their response differs in persons with a history of melanoma when compared to that of healthy individuals. By using laser capture microdissection (LCM) to isolate a pure population of melanocytes from a small area of skin that had been intermittingly exposed or un-exposed to physiological doses of solar UVR, we can now report for the first time that the majority of UV-responsive microRNAs (miRNAs) in the melanocytes of a group of women with a history of melanoma are down-regulated when compared to those in the melanocytes of healthy controls. Among the miRNAs that were commonly and significantly down-regulated in each of these women were miR-193b (<i>P</i><0.003), miR-342-3p (<i>P</i><0.003), miR186 (<i>P</i><0.007), miR-130a (<i>P</i><0.007), and miR-146a (<i>P</i><0.007). To identify genes potentially released from inhibition by these repressed UV-miRNAs, we analyzed databases (e.g., DIANA-TarBase) containing experimentally validated microRNA-gene interactions. In the end, this enabled us to construct UV-miRNA-gene regulatory networks consisting of individual genes with a probable gain-of-function being intersected not by one, but by several down-regulated UV-miRNAs. Most striking, however, was that these networks typified well-known regulatory modules involved in controlling the epithelial-to-mesenchymal transition and processes associated with the regulation of immune-evasion. We speculate that these pathways become activated by UVR resulting in miRNA down regulation only in melanocytes susceptible to melanoma, and that these changes could be partially responsible for empowering these cells toward tumor progression.</p></div