DNAReplication: a database of information and resources for the eukaryotic DNA replication community

DNAReplication (at http://www.dnareplication.net) has been set up as a freely available single resource to facilitate access to information on eukaryotic DNA replication. This database summarizes organism-sorted data on replication proteins in the categories of nomenclature, biochemical properties, motifs, interactions, modifications, structure, cell localization and expression, and general comments. Replication concepts are defined and a general model of the steps in DNA replication is presented. Links to relevant websites and homepages of replication labs are provided. The site also has an interactive section where links to recent replication papers are posted and readers are provided with the facility to post comments about each paper. The interactive and links pages are modified weekly and the whole site is updated annually

A simple bypass assay for DNA polymerases shows that cancer-associated hypermutating variants exhibit differences in vitro.

Errors made by DNA polymerases contribute to both natural variation and, in extreme cases, genome instability and its associated diseases. Recently, the importance of polymerase misincorporation in disease has been highlighted by the identification of cancer-associated polymerase variants with mutations in the exonuclease domain. A subgroup of these variants have a hypermutation phenotype in tumours, and when modelled in yeast, they show mutation rates in excess of that seen with polymerase with simple loss of proofreading activity. We have developed a bypass assay to rapidly determine the tendency of a polymerase to misincorporate in vitro. We have used the assay to compare misincorporation by wild-type, exonuclease-defective and two hypermutating human DNA polymerase ε variants, P286R and V411L. The assay clearly distinguished between the misincorporation rates of wild-type, exonuclease dead and P286R polymerases. However, the V411L polymerase showed misincorporation rate comparable to the exonuclease dead enzyme rather than P286R, suggesting that there may be some differences in the way that these variants cause hypermutation. Using this assay, misincorporation opposite a templated C nucleotide was consistently higher than for other nucleotides, and this caused predominantly C-to-T transitions. This is consistent with the observation that C-to-T transitions are commonly seen in DNA polymerase ε mutant tumours

Urban geoscience report : capacity for 3D urban modelling

This report considers opportunities for future 3D urban geology modelling at the BGS. A total of 42 towns and cities in Great Britain were considered in this study, selected based on expected growth areas, e.g. Leeds, Oxford, and/or regionally important urban centres e.g. London, Glasgow. The selected areas also include 13 ‘Cohort 1’ towns identified by the UK Governments Towns Fund, such as Blackpool and Middlesbrough. The review reflects on recent and current 3D urban modelling approaches; considers the nature and complexity of the geology of British towns and cities; evaluates the availability of geological data for 3D modelling and suitable 3D modelling software; and highlights priority areas for innovation. It concludes by providing a series of recommendations for urban geology modelling

Tethered N-Heterocyclic Carbene-Carboranyl Silver Complexes for Cancer Therapy

Silver complexes of tethered N-heterocyclic carbene-carboranyl ligands have been prepared and fully characterized. The first example of silver bonded directly to the cage of o-carborane has been identified in the solid state. The presence of a carboranyl N substituent on the N-heterocyclic carbene significantly enhances the in vitro cytotoxicity of the silver complex against HCT116 p53+/+ and HCT116 p53–/– colon cancer cells in comparison to a phenyl derivative. Conversely, the presence of a carboranyl on the backbone of a xanthine-derived N-heterocyclic carbene decreases the in vitro cytotoxicity of the silver complex in comparison to its phenyl derivative. Stability studies on the xanthine-derived ligands and complexes show that decomposition via deboronation occurs in hydrous dimethyl sulfoxide, which may attribute to the contrasting in vitro behaviors of the carborane-containing complexes

A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia

Squamous dysplasia of the oral cavity indicates increased risk of progression to squamous cell carcinoma (SCC). An important advance would be the development of a minimally invasive assay for identification of oral SCC and dysplasia. We have investigated the suitability in this context of immunostaining oral smears for minichromosome maintainance proteins (MCMs), sensitive and specific biomarkers of cell cycle entry. Immunohistochemical examination of 66 oral tissue samples showed a greater frequency of Mcm-2 expression in surface layers of moderate/severe dysplasia and SCC compared to benign keratosis/mild dysplasia. Immunocytochemistry for Mcm-2/Mcm-5 was performed on 101 oral smears. Conventional smears included 23 from normal mucosa, benign proliferative disease and mild dysplasia, all of which were MCM negative. Of 52 conventional smears of SCC tissue samples, 18 were inadequate. However, MCM-positive cells were present in 33/34 adequate samples. Of 26 liquid-based cytology smears, 19 out of 20 smears from SCC were adequate and all were MCM positive. Six smears from benign lesions were adequate and MCM negative. We conclude that MCMs are promising markers for early detection of oral SCC and dysplasia, particularly in a liquid-based cytology platform. Detection of MCMs would be amenable to automation and potentially applicable in the developing world. Further studies are now warranted

Assessing the effectiveness of retrograde autologous priming of the cardiopulmonary bypass machine in isolated coronary artery bypass grafts

Introduction Currently, around 35–80% of patients undergoing cardiac surgery in the UK receive a blood transfusion. Retrograde autologous priming (RAP) of the cardiopulmonary bypass circuit has been suggested as a possible strategy to reduce blood transfusion during cardiac surgery. Methods Data from 101 consecutive patients undergoing isolated coronary artery bypass grafts (where RAP was used) were collected prospectively and compared with 92 historic patients prior to RAP use in our centre. Results Baseline characteristics (ie age, preoperative haemoglobin [Hb] etc) were not significantly different between the RAP and non-RAP groups. The mean pump priming volume of 1,013ml in the RAP group was significantly lower (p&lt;0.001) than that of 2,450ml in the non-RAP group. The mean Hb level at initiation of bypass of 9.1g/dl in patients having RAP was significantly higher (p&lt;0.001) than that of 7.7g/dl in those who did not have RAP. There was no significant difference between the RAP and non-RAP groups in transfusion of red cells, platelets and fresh frozen plasma, 30-day mortality, re-exploration rate and predischarge Hb level. The median durations of cardiac intensive care unit stay and in-hospital stay of 1 day (interquartile range [IQR]: 1–2 days) and 5 days (IQR: 4–6 days) in the RAP group were significantly shorter than those of the non-RAP group (2 days [IQR: 1–3 days] and 6 days [IQR: 5–9 days]). Conclusions In the population group studied, RAP did not influence blood transfusion rates but was associated with a reduction in duration of hospital stay. </jats:sec

UKGEOS: Glasgow Geothermal Energy Research Field Site (GGERFS): initial summary of the geological platform

The preferred second UKGEOS site is at Clyde Gateway, in the east end of Glasgow, Scotland. The focus of this, the Glasgow Geothermal Energy Research Field Site (GGERFS), is on characterising and monitoring the subsurface for minewater and hot sedimentary aquifer geothermal energy, and for cooling and heat storage. This report details BGS data and knowledge at late 2016, to define initial characterisation of the ‘geological platform’ relevant for the planning of a geothermal research facility and associated environmental baseline monitoring. The report covers knowledge of the bedrock and superficial deposits geology, abandoned coal mines, hydrogeology, geothermal datasets, geochemistry, remote sensed data, seismicity, stress fields, engineering geology and rock property datasets. BGS holds a great deal of legacy borehole, mining and geochemistry data and has updated existing bedrock and superficial deposits models of the area. However, deep borehole and seismic data are lacking to define the geology and structure of the area below a few hundred metres. Hydrogeological and temperature data are also lacking for the bedrock strata. Regional datasets and knowledge have (and can be further) used to reduce uncertainty and risk in these aspects of the geological characterisation