Geology and land-use planning: Great Broughton-Lamplugh area, Cumbria. Part 2, land-use planning

This report is one of two which describes the results of a research project funded jointly by the Department of the Environment and the British Geological Survey. The objectives of the project were to provide an up-to-date geological database for the Great Broughton-Lamplugh area as a foundation for land use and development, effective future geological research and the safeguarding of mineral resources. Part 1 (BGS Technical Report WA/92/54), available separately, describes the geology. The results, with particular emphasiso n landuse planning, are described here. The present study is the third DOE sponsored applied geological mapping project in Cumbria; previous surveys have covered the Workington and Maryport, and Dearham and Gilcrux areas

Effects of old landfills on groundwater quality. Phase 2, investigation of the Thriplow landfill 1996–1997

Disused sand and gravel excavations overlying the major Chalk aquifer at Thriplow in Cambridgeshire have been filled with domestic waste in two phases. One area (Phase 1) was filled between 1957–77 with little compaction of the refuse and was left uncapped, while Phase 2 was deposited between 1981–87 and capped with clay. Aerial photography and surface resistivity surveys indicate that the site geometry is complex, with several phases of landfilling into excavations of differing depths. Drilling through the waste indicates that leachate production and waste stabilisation proceed at different rates in capped and uncapped landfills. Analysis of leachate obtained by centrifugation or squeezing appears to give more insight into the pollution potential than do leach tests with distilled water. The Biological Methane Potential (BMP) of the waste appears to be related to the quantity of decomposable material but the chemical oxygen demand (COD) values are distorted by the presence of reduced metals. Too few boreholes have been drilled to define the leachate source in terms of its spatial distribution and little is known of how its composition has changed with time. However, hydraulic conductivity measurements on the landfill caps suggest that it is sufficiently permeable for all rainfall to potentially infiltrate the waste. Boreholes outside the landfill penetrate the Upper and Lower Chalk, and identify the Melbourn Rock and underlying Plenus Marls at the junction of the two formations about 20 m below ground level (bgl). Surface resistivity surveys using the BGS RESCAN system, confirm aerial photographs of the extent of the landfill and also suggest that leachate has migrated beyond the base of the landfill. Evidence of leachate migration in pre-existing screened boreholes completed above and below the Plenus Marls suggests that leachate is flowing above the Plenus Marls. Hydraulic head measurements whilst drilling a borehole to the base of the lower Chalk approx. 70 m bgl revealed the potential for upward groundwater flow through the Plenus Marls. Thus, previously-drilled boreholes penetrating the Plenus Marls are expected to recharge upwards into the shallow aquifer above the Plenus Marls diluting any leachate in the upper aquifer and distorting the flow regime. Several of these boreholes have subsequently been modified to stem the flow across the Plenus Marls. One borehole down-gradient to the west of the site revealed a large thickness of drift composed of both sand and clay rich material. This suggests the existence of a buried channel, the hydrogeological significance of which has yet to be assessed. Groundwater chemistry appears to be influenced by three major factors. (a) the landfill leachate (b) the composition of shallow groundwater in the top 10 m of the Chalk, and (c) the composition of water from the Lower Chalk. Limited groundwater monitoring data appear to display a cyclic variation in chloride concentration. The origin for this is not clear but it may correlate with cyclic variations in groundwater levels when the water table rises into the waste. Cyclic flushing of the landfill may release leachate into the aquifer giving rise to pulses of chloride. Alternatively changes in chloride may arise by the changing direction of groundwater flow which as yet has not been assessed. A conceptual hydrogeological model in which flow is limited to above the Plenus Marls has been used to develop a more appropriate groundwater flow and solute transport model. However, the model lacks data on aquifer properties, on contaminant inputs concentrations, fluxes and spatial variations, and there is a paucity of monitoring data for calibration. Nonetheless preliminary transport modelling using an equivalent porous medium approach shows that an effective porosity of about 5% best fits the regional data. Since this is much less than the total porosity of about 40% for the Chalk, it would appear that only part of the Chalk is available for flow but that matrix diffusion could play an important role in leachate attenuation. Discrete fracture modelling using the FRACTRAN code has allowed some scoping to be made of the hydraulic properties of the aquifer by comparison with chloride hydrographs, but these again need to be better conditioned by in-situ measurement of fracture distributions and transmissivities. A number of additional activities are required to improve the understanding of flow and contaminant transport at the site. These include better spatial definition of the waste distribution, improved data on the hydraulic properties of the Chalk aquifer, and the use of automatic monitoring to record temporal changes in groundwater chemistry and groundwater levels

Differences in the pattern and regulation of mineral deposition in human cell lines of osteogenic and non-osteogenic origin

Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro in response to osteogenic medium (OM). It is unclear, however, whether this property is specific to cells of mesenchymal origin. We analysed the OM response in 3 non-osteogenic lines, HEK293, HeLa and NTera, compared to MSCs. Whereas HEK293 cells failed to respond to OM conditions, the 2 carcinoma-derived lines NTera and HeLa deposited a calcium phosphate mineral comparable to that present in MSC cultures. However, unlike MSCs, HeLa and NTera cultures did so in the absence of dexamethasone. This discrepancy was confirmed, as bone morphogenetic protein inhibition obliterated the OM response in MSCs but not in HeLa or NTera, indicating that these 2 models can deposit mineral through a mechanism independent of established dexamethasone or bone morphogenetic protein signalling

Yersinia effectors target mammalian signalling pathways

Animals have an immune system to fight off challenges from both viruses and bacteria. The first line of defence is innate immunity, which is composed of cells that engulf pathogens as well as cells that release potent signalling molecules to activate an inflammatory response and the adaptive immune system. Pathogenic bacteria have evolved a set of weapons, or effectors, to ensure survival in the host. Yersinia spp. use a type III secretion system to translocate these effector proteins, called Yops, into the host. This report outlines how Yops thwart the signalling machinery of the host immune system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73466/1/j.1462-5822.2002.00182.x.pd

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues