An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus

DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses

Historical responsibility for climate change : science and the science-policy interface

Since 1990, the academic literature on historical responsibility (HR) for climate change has grown considerably. Over these years, the approaches to defining this responsibility have varied considerably. This article demonstrates how this variation can be explained by combining various defining aspects of historical contribution and responsibility. Scientific knowledge that takes for granted choices among defining aspects will likely become a basis for distrust within science, among negotiators under the United Nations Framework Convention on Climate Change (UNFCCC), and elsewhere. On the other hand, for various reasons, not all choices can be explicated at all times. In this article, we examine the full breadth of complexities involved in scientifically defining HR and discuss how these complexities have consequences for the science–policy interface concerning HR. To this end, we review and classify the academic literature on historical contributions to and responsibility for climate change into categories of defining aspects. One immediately policy-relevant conclusion emerges from this exercise: Coupled with negotiators’ highly divergent understandings of historical responsibility, the sheer number of defining aspects makes it virtually impossible to offer scientific advice without creating distrust in certain parts of the policy circle. This conclusion suggests that scientific attempts to narrow the options for policymakers will have little chance of succeeding unless policymakers first negotiate a clearer framework for historical responsibility

Diatoms, dissolved silica and biogenic silica dynamics in the Scheldt estuary

info:eu-repo/semantics/publishe

Turbidity Maximum Entrapment of Phytoplankton in the Chesapeake Bay

Estuarine turbidity maxima (ETM) play an impor- tant role in zooplankton and larval fish productivity in many estuaries. Yet in many of these systems, little is known about the food web that supports this secondary production. To see if phytoplankton have the potential to be a component of the ETM food web in the Chesapeake Bay estuary a series of cruises were carried out to determine the biomass distribution and floral composition of phytoplankton in and around the ETM during the winter and spring using fluorometry, high- performance liquid chromatography (HPLC), and microscopy. Two distinct phytoplankton communities were observed along the salinity gradient. In lower salinity waters, biomass was low and the community was composed mostly of diatoms, while in more saline waters biomass was high and the community was composed mostly of mixotrophic dinoflagellates, which were often concentrated in a thin layer below the pycnocline. Phytoplankton biomass was always low in the ETM, but high concentrations of phytoplankton pigment degradation products and cellular remains were often observed suggesting that this was an area of high phytoplankton mortality and/or an area where phytoplankton derived particulate organic matter was being trapped. These results, along with a box model analysis, suggest that under certain hydrodynamic conditions phyto- plankton derived organic matter can be trapped in ETM and potentially play a role in fueling secondary production