Hit-and-run epigenetic editing prevents senescence entry in primary breast cells from healthy donors

Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest. Our data show that the key driver of this phenotype is repression of CDKN2A transcript p16 where myoepithelial cells harbour cancer-like gene expression but do not exhibit anchorage-independent growth. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, which may facilitate tumour initiation

Is the southeastern Adriatic Sea coastal strip an eutrophic area?

This study intends to understand and assess the effects of the discharge from the Buna/Bojana river delta watersheds on the eutrophic status of the southeastern Adriatic Sea, and contrast this area with the northwestern Adriatic region where the Po River dominates the freshwater discharge into the coastal ocean. We compare observations of inorganic nutrients, turbidity, and physical variables from the two regions and use numerical model results to characterize the physical circulation of the two areas. The area affected by the Po River discharge extends at least one hundred kilometers southward from the delta and approximately 20 km offshore. Maximum chlorophyll concentrations typically occur within the river plume. Similarly, in the southeastern Adriatic Sea, the Buna/Bojana River discharge extends northward along the coasts for approximately one hundred kilometers and contains a large maxima in the regional chlorophyll distribution. The two coastal areas tend to have opposing physical forcing processes: the Po River tends to be affected area by northerly to northeasterly winds that cause downwelling, whereas the Buna/Bojana River on the opposite side of the basin is typically characterized by northerly, upwelling favorable winds. However, during the study period, upwelling is not a dominant feature of the circulation and both the shelf slope current (SouthEastern Adriatic e SEAd current) and the along shore currents in the southeastern Adriatic Sea are northward. The along shore current probably dominated by the river runoff is here described for the first time and called the southeastern Shelf Coastal (SESC) current. Under these conditions, primary productivity is high in both regions leading us to conclude that river plume dynamics and the associated nutrient inputs determine the eutrophication status of the coastal strip, regardless of the circulation regime in the southeastern Adriatic Sea area. The Adriatic southeastern coastal area is an eutrophic area that is strongly affected by freshwater inputs particularly from the Buna/ Bojana River system

Is the southeastern Adriatic Sea coastal strip an eutrophic area?

This study intends to understand and assess the effects of the discharge from the Buna/Bojana river delta watersheds on the eutrophic status of the southeastern Adriatic Sea, and contrast this area with the northwestern Adriatic region where the Po River dominates the freshwater discharge into the coastal ocean. We compare observations of inorganic nutrients, turbidity, and physical variables from the two regions and use numerical model results to characterize the physical circulation of the two areas. The area affected by the Po River discharge extends at least one hundred kilometers southward from the delta and approximately 20 km offshore. Maximum chlorophyll concentrations typically occur within the river plume. Similarly, in the southeastern Adriatic Sea, the Buna/Bojana River discharge extends northward along the coasts for approximately one hundred kilometers and contains a large maxima in the regional chlorophyll distribution. The two coastal areas tend to have opposing physical forcing processes: the Po River tends to be affected area by northerly to northeasterly winds that cause downwelling, whereas the Buna/Bojana River on the opposite side of the basin is typically characterized by northerly, upwelling favorable winds. However, during the study period, upwelling is not a dominant feature of the circulation and both the shelf slope current (SouthEastern Adriatic e SEAd current) and the along shore currents in the southeastern Adriatic Sea are northward. The along shore current probably dominated by the river runoff is here described for the first time and called the southeastern Shelf Coastal (SESC) current. Under these conditions, primary productivity is high in both regions leading us to conclude that river plume dynamics and the associated nutrient inputs determine the eutrophication status of the coastal strip, regardless of the circulation regime in the southeastern Adriatic Sea area. The Adriatic southeastern coastal area is an eutrophic area that is strongly affected by freshwater inputs particularly from the Buna/ Bojana River system.Published395-4061.8. Osservazioni di geofisica ambientaleJCR Journalreserve

DNA Methylation Status of Key Cell-Cycle Regulators Such as CDKNA2/p16 and CCNA1 Correlates with Treatment Response to Doxorubicin and 5-Fluorouracil in Locally Advanced Breast Tumors

International audienc