Icebergs in the North Atlantic: Modelling circulation changes and glacio-marine deposition

In order to investigate meltwater events in the North Atlantic, a simple iceberg generation, drift, and melting routine was implemented in a high-resolution OGCM. Starting from the modelled last glacial state, every 25th day cylindrical model icebergs 300 meters high were released at 32 specific points along the coasts. Icebergs launched at the Barents Shelf margin spread a light meltwater lid over the Norwegian and Greenland Seas, shutting down the deep convection and the anti-clockwise circulation in this area. Due to the constraining ocean circulation, the icebergs produce a tongue of relatively cold and fresh water extending eastward from Hudson Strait that must develop at this location, regardless of iceberg origin. From the total amount of freshwater inferred by the icebergs, the thickness of the deposited IRD could be calculated in dependance of iceberg sediment concentration. In this way, typical extent and thickness of Heinrich layers could be reproduced, running the model for 250 years of steady state with constant iceberg meltwater inflow

Life histories of the copepods Pseudocalanus minutus, P. acuspes (Calanoida) and Oithona similis (Cyclopoida) in the Arctic Kongsfjorden (Svalbard)

The year-round variation in abundance and stage-specific (vertical) distribution of Pseudocalanus minutus and Oithona similis was studied in the Arctic Kongsfjorden, Svalbard. Maxima of vertically integrated abundance were found in November with 111,297 ind m−2 for P. minutus and 704,633 ind m−2 for O. similis. Minimum abundances comprised 1,088 ind m−2 and 4,483 ind m−2 in June for P. minutus and O. similis, respectively. The congener P. acuspes only occurred in low numbers (15–213 ind m−2), and successful reproduction was debatable. Reproduction of P. minutus took place in May/June, and stage distribution revealed a 1-year life cycle with copepodids CIII, CIV, and CV as the overwintering stages. Oithona similis exhibited two main reproductive peaks in June and August/September, respectively. Moreover, it reproduced more or less continuously throughout the whole year with all stages occurring during the entire sampling period, suggesting two generations per year. Both species migrated towards greater depth in November, but O. similis preferred to stay longer in the upper 100 m as compared to Pseudocalanus. The reproduction of the two species in Kongsfjorden seemed to be linked to phytoplankton dynamics

Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma

Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O6-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability