Risk factors associated with sustained circulation of six zoonotic arboviruses: a systematic review for selection of surveillance sites in non-endemic areas

Arboviruses represent a signifcant burden to public health and local economies due to their ability to cause unpredictable and widespread epidemics. To maximize early detection of arbovirus emergence in non-endemic areas, surveillance eforts should target areas where circulation is most likely. However, identifying such hotspots of potential emergence is a major challenge. The ecological conditions leading to arbovirus outbreaks are shaped by complex interactions between the virus, its vertebrate hosts, arthropod vector, and abiotic environment that are often poorly understood. Here, we systematically review the ecological risk factors associated with the circulation of six arboviruses that are of considerable concern to northwestern Europe. These include three mosquito-borne viruses (Japanese encephalitis virus, West Nile virus, Rift Valley fever virus) and three tick-borne viruses (Crimean-Congo hemorrhagic fever virus, tick-borne encephalitis virus, and louping-ill virus). We consider both intrinsic (e.g. vector and reservoir host competence) and extrinsic (e.g. temperature, precipitation, host densities, land use) risk factors, identify current knowledge gaps, and discuss future directions. Our systematic review provides baseline information for the identifcation of regions and habitats that have suitable ecological conditions for endemic circulation, and therefore may be used to target early warning surveillance programs aimed at detecting multi-virus and/or arbovirus emergence

Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain

In age-related neurodegenerative diseases, like Alzheimer's and Parkinson's, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm and human cell models for diseases. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated conditional Serf2 knockout mice and found that full-body deletion of Serf2 delayed embryonic development, causing premature birth and perinatal lethality. Brain-specific Serf2 knockout mice, on the other hand, were viable, and showed no major behavioral or cognitive abnormalities. In a mouse model for amyloid-β aggregation, brain depletion of Serf2 altered the binding of structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in the human brain. These results suggest that Serf2 depletion changed the structure of amyloid deposits, which was further supported by scanning transmission electron microscopy, but further study will be required to confirm this observation. Altogether, our data reveal the pleiotropic functions of SERF2 in embryonic development and in the brain and support the existence of modifying factors of amyloid deposition in mammalian brain, which offer possibilities for polymorphism-based interventions. </p

An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis

Review Report: Building C-400 Thermal Treatment 90 Percent Remedial Design Report and Site Investigation, Pgdp, Paducah, Kentucky

On 9 April 2007, the U.S. Department of Energy (DOE) Headquarters, Office of Soil and Groundwater Remediation (EM-22) initiated an Independent Technical Review (ITR) of the 90% Remedial Design Report (RDR) and Site Investigation (RDSI) for thermal treatment of trichloroethylene (TCE) in the soil and groundwater in the vicinity of Building C-400 at the Paducah Gaseous Diffusion Plant (PGDP). The general ITR goals were to assess the technical adequacy of the 90% RDSI and provide recommendations sufficient for DOE to determine if modifications are warranted pertaining to the design, schedule, or cost of implementing the proposed design. The ultimate goal of the effort was to assist the DOE Paducah/Portsmouth Project Office (PPPO) and their contractor team in ''removing'' the TCE source zone located near the C-400 Building. This report provides the ITR findings and recommendations and supporting evaluations as needed to facilitate use of the recommendations. The ITR team supports the remedial action objective (RAO) at C-400 to reduce the TCE source area via subsurface Electrical Resistance Heating (ERH). Further, the ITR team commends PPPO, their contractor team, regulators, and stakeholders for the significant efforts taken in preparing the 90% RDR. To maximize TCE removal at the target source area, several themes emerge from the review which the ITR team believes should be considered and addressed before implementing the thermal treatment. These themes include the need for: (1) Accurate and site-specific models as the basis to verify the ERH design for full-scale implementation for this challenging hydrogeologic setting; (2) Flexible project implementation and operation to allow the project team to respond to observations and data collected during construction and operation; (3) Defensible performance metrics and monitoring, appropriate for ERH, to ensure sufficient and efficient clean-up; and (4) Comprehensive (creative and diverse) contingencies to address the potential for system underperformance, and other unforeseen conditions These themes weave through the ITR report and the various analyses and recommendations. The ITR team recognizes that a number of technologies are available for treatment of TCE sources. Further, the team supports the regulatory process through which the selected remedy is being implemented, and concurs that ERH is a potentially viable remedial technology to meet the RAOs adjacent to C-400. Nonetheless, the ITR team concluded that additional efforts are needed to provide an adequate basis for the planned ERH design, particularly in the highly permeable Regional Gravel Aquifer (RGA), where sustaining target temperatures present a challenge. The ERH design modeling in the 90% RDR does not fully substantiate that heating in the deep RGA, at the interface with the McNairy formation, will meet the design goals; specifically the target temperatures. Full-scale implementation of ERH to meet the RAOs is a challenge in the complex hydrogeologic setting at PGDP. Where possible, risks to the project identified in this ITR report as ''issues'' and ''recommendations'' should be mitigated as part of the final design process to increase the likelihood of remedial success. The ITR efforts were organized into five lines of inquiry (LOIs): (1) Site investigation and target zone delineation; (2) Performance objectives; (3) Project and design topics; (4) Health and safety; and (5) Cross cutting and independent cost evaluation. Within each of these LOIs, the ITR team identified a series of unresolved issues--topics that have remaining uncertainties or potential project risks. These issues were analyzed and one or more recommendations were developed for each. In the end, the ITR team identified 27 issues and provided 50 recommendations. The issues and recommendations are briefly summarized below, developed in Section 5, and consolidated into a single list in Section 6. The ITR team concluded that there are substantive unresolved issues and system design uncertainties, resulting in technical and financial risks to DOE. If PPPO and their remedial team objectively evaluate each issue and recommendation to formulate a project risk mitigation strategy toward remedial implementation, the ITR team believes that issues can be resolved to maximize the potential to successfully achieve the regulatory goals. The review recommendations are intended to maximize contaminant extraction through improvements to the design, assure defensible performance metrics to measure progress and system shutdown, save cost, and improve the probability of successful full-scale implementation. The ITR team gratefully acknowledges the efforts of the PGDP project team and their support of our review process and commends the PGDP project team for their openness and responsiveness to the review comments and information requests